Integrin-blocking polypeptides and uses thereof

ABSTRACT

A series of integrin blockers that present strong angiogenesis inhibiting performance, high integrin affinity and integrin-bonding capacity is provided. This series of integrin blockers can be adopted in treatment of solid tumors and rheumatoid arthritis. Specifically, said series of integrin blockers include polypeptide I, polypeptide II and polypeptide III (see SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3) that can be adopted in treatment of solid tumors and rheumatoid arthritis. This invention also relates to application of these three integrin-blocking polypeptides in preparation of anti-tumor drugs, wherein the tumors that can be treated include those primary or secondary cancers originated from head and neck region or other organs such as brain, thyroid, esophagus, pancreas, lung, liver, stomach, breast, kidney, gallbladder, colon, rectum, ovary, cervix, uterus, prostate, bladder and testicle, as well as melanoma and sarcomas.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation Application of U.S. patentapplication Ser. No. 14/368,960 filed on Jun. 24, 2014 entitledINTEGRIN-BLOCKING POLYPEPTIDES AND USES THEREOF, which granted as U.S.Pat. No. 9,458,203, which claims priority to PCT Application No.PCT/CN2012/087465, having a filing date of Dec. 26, 2012, based off ofCN Application No. 201110443052.2 having a filing date of Dec. 27, 2011,the entire contents of which are hereby incorporated by reference.

FIELD OF TECHNOLOGY

This follows relates to the pharmaceutical field, specifically to aseries of integrin blockers that present strong angiogenesis-inhibitingperformance, high integrin affinity and integrin-bonding capacity. Thisseries of integrin blockers include two polypeptides and can be adoptedin treatment of solid tumors and rheumatoid arthritis.

BACKGROUND

Unlimited proliferation, infiltration and metastasis constitute thecharacteristics of a malignant tumor, and also the major reasons leadingto failed treatment and death. Therefore, effective control ofproliferation, infiltration and metastasis is the essential measure toimprove prognosis and survival rate of tumor-bearing patients. In 1971,Folkman firstly pointed out that the growth of tumor relies onangiogenesis, which is the morphological basis for tumor proliferationand metastasis in that it not only provides nutrition required for tumorgrowth, but also transfers numerous tumor cells to the host's otherorgans and consequently results in metastasis. Most of malignant solidtumors, such as ovarian cancer, liver cancer, cervical cancer and breastcancer, are angiogenesis-dependent. As the new blood vessels formedthrough angiogenesis can on the one hand provide nutrition and oxygenfor the tumor, and on the other hand act as important channel for tumormetastasis, inhibiting the process of angiogenesis is one of the mostimportant measures to fight against cancer.

Integrins are a type of receptors widely found on the cell surface. Theycan induce adhesion of vascular endothelial cells and tumor cells, andfacilitate angiogenesis and tumor metastasis by means of mediatinginteraction between intracelluar cytoskeletal proteins and extracellularmatrix molecules. Currently, at least 8 integrins (α1β1, α2β1, α3β1,α6β1, α6β4, α5β1, αvβ3, αvβ5) have been found closely related to tumorangiogenesis, among them αvβ3 being the most important. Integrin αvβ3 isalso called VN receptor. It is a transmembrane heterodimer glycoproteinconsisting of an αv subunit (CD51, 150 kD) and a β3 subunit (CD61, 105kD). Integrin αvβ3 is expressed in many cell types and can combine witha variety of ligands during multicellular activities; therefore, it isextensively involved in tumor angiogenesis, infiltration and metastasis.It has been found that integrin αvβ3 can recognize the sequenceArg-Gly-Asp (RGD) in its ligands, which means that an RGD-containingpolypeptide can function as an integrin antagonist and inhibitangiogenesis by means of reducing the expression of adhered molecules onthe cell surface and mediating intracellular signal transduction. Thiseventually slows down tumor growth and metastasis. In other words,integrin-targeting polypeptides can block intracellular signalingpathways downstream of the integrin and effectively inhibit tumor growthand metastasis by means of slowing down angiogenesis. These featuresprovide integrin-targeting polypeptides very promising prospects intumor treatment.

Currently, some integrin blockers have been developed out on theinternational market and are undergoing the phase II clinical trial.However, no such products are seen on the Chinese market. It is of greatnecessity to develop this type of drugs with China's independentintellectual property. The Chinese patent “Angiogenesis-inhibitingPolypeptides and Preparation and Application Thereof′ (ZL200610039298.2) disclosed a series of polypeptides obtained throughrestructuring and modifying the 6-49 amino acids on the integrinsequence. In contrast with endostatin, the restructured polypeptidespresent higher in vivo activity and tumor-targeting performance. In thiscited patent, several integrin inhibitors were introduced, two of whichwereArg-Gly-Asp-Phe-Gln-Pro-Val-Leu-HiArg-Gly-Asp-Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Phe (SEQ ID NO: 4) (EDSM-1 for short)and Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Phe-Gly-Gly-Gly-Gly-Ala-Cys-Arg-Gly-Asp-Cys-Phe-Cys(SEQ ID NO: 5) (EDSM-2 for short). Both of the sequences contain anintegrin ligand sequence, consisting of Arg-Gly-Asp andGly-Gly-Gly-Gly-Ala-Cys-Arg -Gly-Asp-Cys-Phe-Cys (SEQ ID NO: 6), and anangiogenesis-inhibiting sequence, namely,Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Phe(SEQ ID NO: 7). The above mentioned patent only conducted preliminaryresearches on cloning of polypeptides EDSM-1 and EDSM-2, construction ofprokaryotically expressed vectors, and the application of EDSM-1 intreatment of liver cancer and gastric cancer. In contrast, the presentinvention, on the basis of further studies on the endostatin sequence,found out that the 6-48 amino acids on the integrin sequence demonstrateeven better angiogenesis-inhibiting function, and then tried to modifythis angiogenesis-inhibiting sequence, namely, Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala (SEQ ID NO:1), by adding an integrin ligand sequence (Arg-Gly-Asp-Gly-Gly-Gly-Gly)(SEQ ID NO: 14) to its N-terminal and C-terminal ends respectively. Themodification results in two new integrin blockers, namely, polypeptideII (Arg-Gly-Asp-Gly-Gly-Gly-Gly-Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala) (SEQ IDNO: 2) and polypeptide III(Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Gly-Gly-Gly-Gly-Arg-Gly-Asp) (SEQ ID NO: 3). Thesenewly designed polypeptides, can on the one hand effectively bind to theintegrin subtype specifically expressed by tumors as the RGD(Arg-Gly-Asp) sequence contained in the integrin ligand sequence cantargetedly recognize the integrin, and on the other hand successfullyinhibit tumor growth and metastasis by means of inhibiting the processof angiogenesisp, a function realized by the angiogenesis-inhibitingsequence contained in them. Therefore, both polypeptide II andpolypeptide III demonstrate strong tumor-targeting performance and highintegrin affinity simultaneously. It has been found that they exhibitdesirable therapeutic effect on many types of tumors, which means theyhave a wide range of indications and entail great social benefits andmarket potential.

Rheumatoid arthritis (RA) is one of the commonest autoimmuneinflammatory arthropathies and major causes for disability. It is achronic, symmetrical multi-synovial arthritis of unknown etiology. Theincidence rate of RA is about 0.5%-1.0% throughout the world and about0.4% in China. It can attack people at any age, but the risk goes higherwith the increase of age. In addition, RA is closely related to gender,and the male to female incidence ratio is 1:3. The female at the age of45-55 are at the highest risk. The initial symptoms of RA areprogressive pain and swelling in hands and wrists, particularly theswelling at the back of wrists. Though such symptoms can be relievedwith common symptomatic treatments, they tend to reappear repeatedly dueto irregular or underdosed medication. With the development of thedisease, progressive stiffness of joints may appear early in the morningand usually lasts for more than one hour, meanwhile, some jointdysfunctions may also appear.

As is mentioned above, the etiology and pathogenesis of RA remainunknown, and its basic pathological manifestations include vasculitisand synovitis. When RA attacks, a layer of pannus forms on the synovialmembrane due to angiogenesis, which consequently results in thickeningof synovial membrane, increase of exudate, release of various cytokines,cartilage destruction and bone erosion. It can also affect surroundingtissues, such as muscular compartments, ligaments, tendon sheaths andmuscles, and finally affect the stability of joints and lead to jointdeformation and disability. The RA vasculitis may attack other organsthroughout the body and manifests itself as a systemic disease.

Currently, drugs for RA treatment can be categorized into two types:symptom-controlling drugs and disease-controlling drugs. Thesymptom-controlling drugs can be further divided into 4 groups: 1.NSAIDs, long regarded as first-line anti-RA agents; there are more thandozens of NSAIDs available on the Chinese market; 2. glucocorticoids,very good anti-inflammatory agents; but they cannot significantlyimprove the symptoms and will lead to many serious side effects if beingused alone for a long time. They can be used, however, in the short termin moderate dose before the slow-onset agents take effect, and would benecessary to form combined medication with the second-line agents inpulse therapy of RA flare-ups, particularly for those patients withextra-articular manifestations; 3. slow-onset, anti-rheumatic drugs,usually regarded as second-line agents, including antimalarials, sodiumaurothiomalate (gold), penicillamine and sulfasalazine; they take effectconsiderably slowly, but have positive functions in improving theoverall condition of RA patients. They are also called disease-modifyingantirheumatic drugs (DMARDs); 4. immunosuppressants, includingmethotrexate, cyclophosphamide, azathioprine, tripterygium andsinomenine, etc.

Angiogenesis is one of the main histological characteristics ofrheumatoid arthritis. It causes hyperplasia of synovial membrane andinfiltration of inflammatory cells—the basis for the formation of pannusand final destruction of joints. Due to angiogenesis, newly-formed bloodvessels invade the joint cartilage, which under healthy conditionscontains no blood vessels. The invasion of blood vessels leads to theerosion of cartilage, pain and eventually deformation of the wholejoint. Also due to angiogenesis, the thickness of patients' synovialmembrane increases. Normally, the inner layer of synovial membrane in ahealth people contains only 1-2 layers of cells; however, it wouldincrease to 4-10 layers (sometimes 20 layers) of cells when RA attacks.These increased cells are not only in great quantity, but also extremelyactive. They can secrete a large quantity of cytokines, signalingmolecules and proteases, all of which accelerate the process of jointdestruction. In addition, there are a large quantity of inflammatorycells, such as T cells, B cells and monocytes infiltrating in thesynovial membrane of RA patients.

Under normal physiological conditions, angiogenesis is strictlyregulated and is a necessary process particularly important forreproduction, fetal development, tissue repair and wound healing. Italso takes place under many pathological conditions, including growthand metastasis of tumors, inflammatory disorders such as RA, psoriasis,osteoarthritis, inflammatory bowel disease (IBD, including Crohn'sdisease and ulcerative colitis) and others.

Integrin αvβ3 can recognize the Arg-Gly-Asp (RGD) sequence in ligandmolecules and bind with a variety of ligands during the multicellularactivities. These features enable it to participate in such tumorprocesses as angiogenesis, infiltration and metastasis as well as otherphysiological and pathological processes such as inflammation, woundhealing, blood coagulation, etc. Therefore, polypeptides bearing the RGDsequence can function as integrin antagonists, and the RGD sequence canbe adopted as a vector, targetedly delivering therapeutic polypeptidesto the endothelium of newly generated blood vessels so that thoseangiogenesis-related diseases can be effectively treated. TheRGD-bearing, angiogenesis-inhibiting polypeptides can not only block thepathways of oxygen and nutrients to the synovial membrane by inhibitingangiogenesis, but also directly lead to degeneration of blood vesselstherein. Therefore, they can inhibit hyperplasia of synovial membrane ofRA patients. In short, inhibition of angiogenesis is an essential stepfor treatment of RA, while the proliferation and migration ofendothelial cells are two crucial mechanisms for angiogenesis.

The RGD (Arg-Gly-Asp) sequence contained in polypeptide II andpolypeptide III enables these polypeptides to realize effectivecombination with integrins. Such a combination on the one hand inhibitsthe interaction between intracellular cytoskeletal proteins andextracellular matrix molecules, and on the other hand inhibits thecell-cell adhesion and the adhesion between cells and extracellularmatrix. The intercellular signaling as well as signal transductionbetween cells and extracellular matrix are consequently blocked, andangiogenesis is therefore inhibited. Meanwhile, there also exists anangiogenesis-inhibiting sequence in the above mentioned polypeptides.Researchers have found that this sequence presents high effect ininhibiting angiogenesis—a feature bearing great significance intreatment of RA and other similar diseases. In short,Integrin-inhibiting polypeptides demonstrate desirable performance intreating RA by targeting at RA's angiogenesis process. This provides anew orientation for developing new anti-RA drugs.

The newly designed polypeptides disclosed in the present invention,namely, polypeptide II and polypeptide III, present strongintegrin-targeting performance and high integrin affinity. Thepreliminary research has indicated that polypeptide II and polypeptideIII can inhibit the proliferation and migration of endothelial cells aswell as capillary formation; with flow cytometry analysis, it detectedout that the function target of polypeptide II and polypeptide III isintegrin αvβ3. Later research also found out that polypeptide II andpolypeptide III can inhibit the formation of capillary structures ofrats' aortic rings, and with the cell adhesion assay, it further provedthat the function target of the polypeptides is integrin αvβ3, andconcluded that the polypeptides can be adopted in treatment of RA. Theseconclusions broaden the indication range of said polypeptides andhighlight their social benefits and market potential.

SUMMARY

One aspect relates to verifying the therapeutic effect of a series ofpolypeptides, including polypeptide I, polypeptide II and polypeptideIII, on solid tumors and RA, and to broaden the indication range ofthese integrin inhibitors.

A series of integrin-blocking polypeptides, their amino acid sequenceis:X-Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Y(SEQ ID NO: 17), wherein the X sequence can be missing, Arg-Gly-Asp,Arg-Gly-Asp-Gly-Gly-Gly-Gly (SEQ ID NO: 14),Ala-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (SEQ ID NO: 15), orAla-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys-Gly-Gly-Gly-Gly (SEQ ID NO: 16);and the Y sequence can be missing, Arg-Gly-Asp,Arg-Gly-Asp-Gly-Gly-Gly-Gly (SEQ ID NO: 14),Ala-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (SEQ ID NO: 15) orAla-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys-Gly-Gly-Gly-Gly (SEQ ID NO: 16).The series of integrin-blocking polypeptides as defined above, whereinsaid amino acid sequence is:

polypeptide I:Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala (SEQ ID NO: 1);

polypeptide II:Arg-Gly-Asp-Gly-Gly-Gly-Gly-Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala (SEQ ID NO: 2);

polypeptide III:Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Gly-Gly-Gly-Gly-Arg-Gly-Asp (SEQ ID NO: 3);

polypeptide IV:Ala-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys-Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala (SEQ ID NO: 8);

polypeptide V:Ala-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys-Gly-Gly-Gly-Gly-Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala(SEQ ID NO: 9);polypeptide VI:Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Arg-Gly-Asp (SEQ ID NO: 10);polypeptide VII:Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Gly-Gly-Gly-Gly-Ala-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys(SEQ ID NO: 11);polypeptide VIII:Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Ala-Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (SEQ ID NO: 12);polypeptide IX:Arg-Gly-Asp-Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala (SEQ ID NO:13), including an effective amountof salts (or if necessary, pharmaceutically acceptable vectors orexcipients) that can be accepted by said polypeptides.

The application of integrin blockers as defined in claims 1 or 2 inpreparation of anti-tumor drugs, wherein the tumors that can be treatedthereby include those primary or secondary cancers originated from headand neck region or other organs such as brain, thyroid, esophagus,pancreas, lung, liver, stomach, breast, kidney, gallbladder, colon,rectum, ovary, cervix, uterus, prostate, bladder and testicle, as wellas melanoma and sarcomas.

The application of integrin blockers as defined in claims 1 or 2 inpreparation of drugs for treating or preventing rheumatoid arthritis.

The method for preparing integrin blockers as defined claims 1 or 2,wherein said polypeptides are obtained by means of solid-phase synthesisor recombination of expression vectors.

Integrin blockers as defined in claim 1 or 2, wherein the adjuvantadopted for covalent connection of polypeptides is bovine serum albumin(BSA), human serum albumin (HSA) or polyethylene glycol (PEG).

The application of integrin blockers in preparation of anti-tumor drugsas defined in claim 4, wherein a variety of routes for administering thepharmaceutical composite can be adopted in treatment of primary orsecondary cancers, melanoma and sarcomas; said routes include hypodermicinjection, intramuscular injection, intravenous injection or drip, oraladministration (in the form of pills, capsules, etc.) and nasal spray.

1. The prior patent (ZL200610039298.2) cited in the present inventiondisclosed that the 6-49 amino acids on the endostatin sequence presentedgood anti-tumor performance. The present invention, on the basis of thisfinding, has conducted extensive researches and finally found that the6-48 amino acids (namely, polypeptide I, EDSM for short, see SEQ IDNO: 1) on the endostatin sequence presented even better anti-tumorperformance; it also found that polypeptide I had excellent performancein treatment of rheumatoid arthritis, which consequently broadened theindication range of the polypeptide. In addition, as the newly foundpolypeptide is one amino acid shorter than the sequence disclosed in theprior patent, the cost for synthesizing it is comparatively lower, whichmeans the present invention bears better social benefits and marketpotential.

Polypeptide II and polypeptide III are two amino acid sequences newlydesigned in the present invention. No patent rights have been authorizedthroughout the world on these two polypeptide sequences. In contrastwith the cited patent (ZL200610039298.2), wherein the number of aminoacids in sequence EDSM-1 and sequence EDSM-2 is 47 and 55 respectively,polypeptide II and polypeptide III disclosed in the present inventionwere undergone the following restructuring: a sequence containing fourGlycines is added between the integrin ligand sequence (RGD) and theangiogenesis-inhibiting sequence. As far as EDSM-1 is concerned, thisrestructuring further increases the activity of EDSM-1 by enhancing itsflexibility and facilitating the integrin ligand sequence (RGD) tocombine the target; as far as EDSM-2 is concerned, this restructuringreduces the number of amino acids on the sequence while keeping itsanti-tumor activity intact, which means it would greatly reduce theproduction cost. Besides, the present invention has also found out thatpolypeptide II and polypeptide III present desirable effect in treatmentof rheumatoid arthritis, which consequently broadens their indicationrange and highlights their social benefits and market potential.

2. Introduction to the Pharmacological Mechanism of the Polypeptides

Researches have shown that on the one hand polypeptide I demonstrateshigh effect in inhibiting tumor angiogenesis and progression ofrheumatoid arthritis, and on the other hand the argnine-glycine-asparticacid (RGD) sequence is one of important ligands of integrin, which meansthat the RGD-containing peptide Gly-Gly-Gly-Gly-Arg-Gly-Asp (SEQ ID NO:35) can specifically recognize integrin. In view of these findings, thepresent invention discloses two integrin-blocking polypeptides preparedthrough combining the sequence Gly-Gly-Gly-Gly-Arg-Gly-Asp (SEQ ID NO:35), which presents high integrin affinity and high integrin-bondingcapacity due to the RGD sequence contained therein, with both theN-terminal and C-terminal ends of the angiogenesis-inhibiting sequence(Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala)(SEQ ID NO: 1) respectively. Both polypeptides so constructed, namely,polypeptide II (Arg-Gly-Asp-Gly-Gly-Gly-Gly-Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala)(SEQ ID NO: 2) and polypeptide III(Phe-Gln-Pro-Val-Leu-His-Leu-Val-Ala-Leu-Asn-Ser-Pro-Leu-Ser-Gly-Gly-Met-Arg-Gly-Ile-Arg-Gly-Ala-Asp-Phe-Gln-Cys-Phe-Gln-Gln-Ala-Arg-Ala-Val-Gly-Leu-Ala-Gly-Thr-Phe-Arg-Ala-Gly-Gly-Gly-Gly-Arg-Gly-Asp) (SEQ ID NO: 3) contain 50 amino acids. Thesetwo polypeptides on the one hand can inhibit the expression of moleculesadhering to the cell surface and the intracellular signal transductiondue to existence of the RGD sequence that presents desirable infinityand bonding capacity specifically targeting at integrin αvβ3, and on theother hand can inhibit tumor growth and metastasis by inhibiting tumorangiogenesis—a function of the angiogenesis-inhibiting sequence theycontain.

As is indicated by many researches, both in and outside China, tumors,even those of the same histological type and at the same degree ofdifferentiation, may present different sensitivity toward the same drug.Therefore, a procedure to screen the anti-tumor spectrum is neededduring the development of a new anti-tumor drug. During this procedure,experiments are conducted to identify the therapeutic effect of a newdrug on different tumors—it may have high effect on specific tumorswhile have low or even no effect on others. With a large quantity ofexperiments, the inventor of the present invention found out that theintegrin blockers have a definitive function target; they on the onehand can significantly inhibit the migration, proliferation andcapillary formation of human umbilical vein endothelial cells (HUVECs)as well as the proliferation of some types of tumor cells under in vitroconditions, and on the other hand demonstrate high anti-tumor effectunder in vivo conditions. In addition, they present fewer side effects,smaller effective dose and less production cost in comparison with someother anti-tumor drugs. The method for preparing the integrin-blockingpolypeptides disclosed in the present invention is reasonably designedand enjoys high feasibility. The drug prepared with this method can beapplied in treatment of various solid tumors. This enormously expandsthe therapeutic spectrum of these integrin blockers, which on the onehand provides a new perspective for developing anti-tumor drugs of thesame kind, and on the other hand entails great social benefits andmarket potential.

The RGD sequence contained in polypeptide II and polypeptide IIIdisclosed in the present invention can targetedly inhibit the activityof endothelial cells of newly generated blood vessels during theformation of pannus in RA patients; therefore, this process caneffectively inhibit angiogenesis and be adopted in prevention andtreatment of RA. With a large quantity of experiments, the inventor ofthe present invention found out that polypeptide II and polypeptide IIIcan effectively inhibit the development of adjuvant-induced RA in ratsand collagen-induced RA in DBA/1 mice. The in vivo experiments haveproved that this series of polypeptides have prominent effect intreatment of RA; they also demonstrate such advantages as few sideeffect, small effective dose and low production cost. The method forpreparing the integrin-blocking polypeptides disclosed in the presentinvention is reasonably designed and enjoys high feasibility. The drugprepared with this method can be applied in prevention and treatment ofRA. This enormously expands the therapeutic spectrum of these integrinblockers, which on the one hand provides a new perspective fordeveloping anti-RA drugs of the same kind, and on the other hand entailsgreat social benefits and market potential.

BRIEF DESCRIPTION

Some of the embodiments will be described in detail, with reference tothe following figures, wherein like designations denote like members,wherein:

FIG. 1 expression of integrin αv and integrin β3 in Bel-7402 cellscharacterized by Western blotting;

FIG. 2 combination between integrin-blocking polypeptide II and thetarget characterized by flow cytometry; and

FIG. 3 combination between integrin-blocking polypeptide III and thetarget characterized by flow cytometry.

DETAILED DESCRIPTION Embodiment 1 Synthesization and Detecting Measuresof Integrin-Blocking Polypeptides

The solid-phase synthesis was adopted to synthesize polypeptide I,polypeptide II, and polypeptide III. The synthesized products werepurified with the high performance liquid chromatography (HPLC), andthen the mass spectrometry (MS) and the reversed phase high performanceliquid chromatography (RP-HPLC) were adopted to determine the molecularweight and purity of synthesized polypeptides respectively.

Taking Fmoc-Phe (Otbu)-wang resin or Fmoc-Arg (Otbu)-CTC resin as thestarting material for the solid-phase synthesis of polypeptide I,Fmoc-Arg (Otbu)-wang resin or Fmoc-Arg (Otbu)-CTC resin as the startingmaterial for the solid-phase synthesis of polypeptide II, and Fmoc-Phe(Otbu)-wang resin or Fmoc-Phe (Otbu)-CTC resin as the starting materialfor the solid-phase synthesis of polypeptide III; adopting the protectedamino acids to consecutively synthesize peptides containing 2 to 43/50amino acids; washing the product when the synthesis process wascompleted; after the cleavage and post-treatment processes, the crudeproduct of polypeptide II/polypeptide III was obtained. Dissolving thecrude product, purifying it with a preparative HPLC twice, and thenfreeze-condensing the product to obtain the pure polypeptideII/polypeptide III. The method adopted here can not only ensure highsynthesis efficiency but also improve the product purity.

1. steps of peptide synthesis (including formation of the peptidecontaining 2 to 43/50 amino acids):

polypeptide I: pouring an appropriate amount of Fmoc-Phe(Otbu)-wangresin or Fmoc-Arg (Otbu)-CTC resin into a glass sand-core reactioncolumn, then adding in an appropriate amount of CH₂Cl₂ to realize fullexpansion of the resin.

polypeptide II: pouring an appropriate amount of Fmoc-Arg(Otbu)-wangresin or Fmoc-Arg (Otbu)-CTC resin into a glass sand-core reactioncolumn, then adding in an appropriate amount of CH₂Cl₂ to realize fullexpansion of the resin.

polypeptide III: pouring an appropriate amount of Fmoc-Phe(Otbu)-wangresin or Fmoc-Phe (Otbu)-CTC resin into a glass sand-core reactioncolumn, then adding in an appropriate amount of CH₂Cl₂ to realize fullexpansion of the resin.

-   -   a. DECAPPING: adding in an appropriate amount of        hexahydropyridine/dimethylformamide (DMF) solution for the        decapping process, draining off the decapping reagent after a        period of reaction and then washing the resin with DMF; adding        in an appropriate amount of the decapping reagent again to        remove the Fmoc protecting group.    -   b. WASHING: draining off the decapping solution, washing the        resin with DMF several times in order to sufficiently rinse off        by-products.    -   c. CONDENSING: dissolving the protected amino acids and the        activator in DMF and the condensing reagent, evenly stirring the        mixture to guarantee sufficient reaction therein.    -   d. WASHING: draining off the reaction solution, washing the        resin with DMF several times in order to sufficiently rinse off        by-products.

The peptide cleavage contained the following steps:

First, loading the drained-off resin into a round-bottom flask; then,adding in the cleavage reagent for sufficiently splitting the newlysynthesized 50-AA intermediate sequence; finally, separating the resinfrom the polypeptide with a sand-core funnel. The volume ratio of thecomponents contained in said cleaving reagent was trifluoroacetic acid(TFA):phenol:water:thioanisole:ethylene diamine tartrate(EDT)=88-92:2.5-3.5:2.5-3.5:1.5-2.5:1.5-2.5.

2. The post-treatment process contained the following steps: first,separating out the polypeptide by adding absolute ether into thecleavage reagent; then, centrifuging the mixture and throwing away thesupernatant; finally, washing the polypeptide with absolute ether anddraining off the absolute ether to obtain the crude polypeptide.

3. The purification process contained the following steps:

-   -   a. DISSOLUTION: dissolving the crude polypeptide in water to        form 5-20 g/l solution and then filtrating the solution with        0.45 μm hybrid membrane.    -   PREPARATION: {circle around (1)} primary purification: running        30%-40% acetonitrile and 60%-70% buffer solution at the flow        rate of 50-100 ml/min for 10-20 min to equilibrate the        preparative column; loading the sample with a metering pump,        setting the baseline and collecting the solution with absorption        value over 200 mv at the UV wavelength of 220 nm; detecting        whether there was the sample in the eluate; adopting gradient        elution, starting at 30%-40% acetonitrile and progressing        linearly at 80-90% acetonitrile over 30-50 min; collecting the        solution with absorption value over 200 mv at the UV wavelength        of 220 nm; converging the part with detected purity over 95% as        the peak and ready for the secondary purification. {circle        around (2)} secondary purification: adopting rotary evaporation        to remove the organic solvent contained in the peak component        collected in the primary purification, loading the sample again        with a metering pump; eluting the column with 30%-40%        acetonitrile and 60%-70% buffer solution at the flow rate of        50-100 ml/min; setting the baseline and collecting the solution        with absorption value over 200 mv at the UV wavelength of 220        nm; detecting whether there was the sample in the eluate;        adopting gradient elution, starting at 30%-40% acetonitrile and        progressing linearly at 80-90% acetonitrile over 30-50 min;        collecting the solution with absorption value over 200 mv at the        UV wavelength of 220 nm; the part with detected purity over 95%        was regarded as qualified.    -   b. CONDENSING, FILTRATING AND FREEZE-DRYING: adopting a rotary        evaporator to condense the qualified solution at 37° C. so that        the residual solvent and eluting water could be removed;        finally, filtrating the solution with 0.22 μm membrane; placing        the filtrate in a freeze-drying plate and freeze-drying the        filtrate in a freeze-dryer.

4. Determination of Purity and Molecular Weight

Collecting the freeze-dried pure product, adopting the reversed phasehigh performance liquid chromatography (RP-HPLC) to determine andanalyze the purity of the polypeptide.

In the present invention, the solid-phase synthesis was successfullyadopted to synthesize the integrin-blocking polypeptides I, II and III.This method presented many advantages such as high repeatability, highpracticality and little pollution. Two types of resin could be used inthe present invention, namely, wang resin and CTC resin; in contrastwith other types of resin, the wang resin demonstrates higher stability,less side reactions, higher yield and better peak shape of the crudeproduct, which mean less production cost; in contrast with other typesof resin, the CTC resin is less affected by reaction temperature andpresents higher reaction rate. The present invention also adoptedRP-HPLC to purify the synthesized polypeptide; in addition, in contrastwith isocratic elution, the gradient elution adopted in the presentinvention presented better separating effect as this mode of elutionguaranteed appropriate retention time during the separation reaction,which consequently led to higher production efficiency and higherpurity.

RESULT: RP-HPLC analysis showed that the purity of the synthesizedpolypeptide I, II and III was 95.39%, 98.41%, 96.40% respectively; theresult met the required purity standard.

Embodiment 2

Analysis of the target of integrin-blocking polypeptide II andpolypeptide III (1) the target integrin αvβ3 expressed by cells wasanalyzed with Western blotting

Digesting Bel-7402 cells in logarithmic phase with 0.25% trypsinase,centrifuging the collected cells at 800 rpm for 5 min; counting thecells and adding in protein extraction solution at the rate of 20 μl per1×10⁵ cells; scattering cells through blow-suctioning and placing themat 4° C. for 30 min for lysis; adding in ¼ volume of 5× protein loadingbuffer and incubating the sample in boiling water for 5-10 min. Taking20 μl protein sample for 10% SDS-PAGE electrophoresis; transferring theprotein from the gel to PVDF membrane through semi-dry electrotransfer(constant current 1 mA/cm², 3 h); dyeing the PVDF membrane in ponceaufor 30 s then decoloring it with dH₂O till clear bands emerged on themembrane; cutting the upper right corner of the membrane to mark theprotein side; blocking the PVDF membrane with blocking buffer at roomtemperature for 1.5 h, and then washing the PVDF membrane with PBST 2-3times, 5-10 min each time. Adding in the primary antibody, incubatingthe sample at 4° C. overnight or 37° C. for 1.5 h, and washing themembrane with PBST 3-5 times, 5-10 min each time. Adding in thesecondary antibody, incubating the sample at 4° C. overnight or 37° C.for 1.5 h, and then washing the membrane with PBST 3-5 times, 5-10 mineach time. In a darkroom (red light allowed), placing the PVDF membraneon preservative film with the protein side upward; evenly dripping aluminescent solution on the membrane surface and waiting for 5 min ofreaction; wrapping the PVDF membrane within preservative film andcutting a piece of X-ray film of the same size as the membrane, andputting them together in a cassette for 0.5-5 min (dependent on thelight intensity of luminescent bands); taking out the X-ray film andputting it into the developing solution till band images emerged on thefilm, then transferring the film into the stop bath (5% glacial aceticacid) and keep the film there for 1 min; washing the film with flowingwater for 1 min and then putting it into the fixing solution till thebackground part of the film turned into transparent; finally, washingthe film with flowing water for 20 min to fixate the images.

(2) Combination Between Integrin-Blocking Polypeptide II/III and theTarget Analyzed with Flow Cytometry

culturing Bel-7402 cells in a culture flask to 80% confluence, thendigesting and collecting cells and washing them with pre-cooled PBSbuffer twice, resuspending cells with 1% BSA-containing PBS buffer for30 min; incubating 2 μl mouse anti-human integrin αvβ3 monoclonalantibody (function-blocking) and 2 μl mouse anti-human integrin α5β1monoclonal antibody (function-blocking) with the cell suspension (1.0μg/μl, 1:200) respectively at 4° C. for 1.5 h; collecting the cells andwashing them with pre-cooled PBS buffer twice, then incubatingpolypeptide II and polypeptide III modified with 100 μl FITC (2 mg/ml)with the cell suspension respectively at 4° C. for 1.5 h; collectingcells after this labeling process and washing them with pre-cooled PBSbuffer twice; resuspending cells with 400 μl PBS buffer and analyzingthem with flow cytometry; detecting intensity of FITC fluorescence withFL1 channel.

RESULTS: Determination of the target (integrin αvβ3) through cellexpression. As is indicated in FIG. 1, integrin αvβ3 was expressed onthe surface of Bel-7402 cells, which means itintegrin αvβ3 can be usedas the combination target for later experiments.

Combination between integrin-blocking polypeptide II/III and the targetanalyzed with flow cytometry. As is shown in FIG. 2, the fluorescenceintensity of integrin-blocking polypeptide II labeled with FITC was80.4% before adding in the antibody and the incubation process; however,it reduced to 13.4% when adding in integrin αvβ3 antibody and 33.2% whenadding in integrin α5β1 antibody. As is shown in FIG. 3, thefluorescence intensity of polypeptide III labeled with FITC was 82.4%before adding in the antibody and the incubation process; however, itreduced to 11.3% when adding in integrin αvβ3 antibody and 25.9% whenadding in integrin α5β1 antibody. The flow cytometry analysis showedthat polypeptide II and polypeptide III could combine with both integrinαvβ3 and integrin α5β1, however, their major combination target wasintegrin αvβ3.

Embodiment 3 Test on Integrin-Blocking Polypeptides in Inhibiting theMigration of Human Umbilical Vein Endothelial Cells (HUVECs)

Diluting 10 mg/ml Matrigel (BD Company, USA) with HUVEC culture mediumat the ratio of 1:2, smearing the Matrigel solution on the membrane of atranswell chamber, and drying at the room temperature. Digesting theHUVECs with trypsinase when they reached the logarithmic phase;collecting the cells and washing them with PBS buffer twice, and thenresuspending the cells with blank HUVECs culture medium. Counting thecells under a microscope, adjusting the cell concentration to 1×10⁵cells/ml. Preparing the testing solution for all groups, and dilutingwith blank HUVECs culture medium to 100 μl. Seeding the cells into thetranswell chamber, 100 μl for each insert, adding also the testingsolution of all groups into the transwell chamber. Adding 0.6 mlendothelial cell culture medium containing 5% fetal calf serum (FCS) and1% endothelial cell growth supplement (ECGS) into the 24-well plate tostimulate cell migration, and incubating the cells in 5% CO₂ at 37° C.for 24 h. Removing the culture solution, fixing the cells with 90%ethanol at the room temperature for 30 min, and staining the cells with0.1% crystal violet at the room temperature for 10 min, then washingwith clean water and gently scraping off non-migrated cells with cottonswabs; observing cells under a microscope and choosing 4 FOVs for cellcounting and photographing. The migration inhibition (MI) rate wascalculated in accordance with the following formula:

${{MI}\mspace{14mu}(\%)} = {1 - {\frac{N_{test}}{N_{control}} \times 100\;\%}}$

wherein N_(test) is the number of migrated cells in the test groupswhile N_(control) is the number of migrated cells in the negativecontrol group.

Conducting the same experiment three times independently, calculatingmean and standard deviation (mean±SD) of all detected data and analyzingthe data with T-test, wherein *P<0.05 refers to significant differenceand **P<0.01 extremely significant difference.

TABLE 1 inhibition effect of integrin-blocking polypeptide I onmigration of HUVECs group dose number of migrated cells MI rate (n = 8)(μg/ml) (mean ± SD) (%) polypeptide I 0.5 979.8 ± 75.3** 18.69% 1 956.0± 78.2** 20.66% 2 961.3 ± 89.5** 20.23% 4 903.5 ± 68.7** 25.02% 8  815.5± 62.32** 32.32% 16 706.3 ± 48.7** 41.39% 32 871.8 ± 67.9** 27.66% 64929.5 ± 99.7** 22.86% ES 20 911.7 ± 33.5** 24.34% control 0 1204.8 ±29.3   — a: * P < 0.05, **P < 0.01.

TABLE 2 inhition effect of integrin-blocking polypeptide II on migrationof HUVECs group dose number of migrated cells MI rate (n = 8) (μg/ml)(mean ± SD) (%) polypeptide II 0.13 875.0 ± 35.3** 24.44% 0.25 800.7 ±64.8** 30.85% 0.5 685.7 ± 32.5** 40.78% 1 611.0 ± 74.1** 47.24% 2 600.3± 39.3** 48.15% 4 531.5 ± 72.6** 54.10% 8 348.8 ± 39.9** 69.87% 16 460.1± 97.3** 60.27% ES 20 880.2 ± 33.3** 23.99% control — 1158.0 ± 54.5**  —a: * P < 0.05, **P < 0.01.

TABLE 3 inhibition effect of integrin-blocking polypeptide III onmigration of HUVECs group dose number of migrated cells MI (n = 8)(μg/ml) (mean ± SD) (%) polypeptide III 0.13 787.1 ± 46.3** 23.08% 0.25595.7 ± 29.3** 41.78% 0.5 490.7 ± 17.1** 52.04% 1 237.6 ± 19.0** 76.78%2 384.1 ± 43.0** 62.46% 4 482.3 ± 19.2** 52.86% ES 20 866.0 ± 27.2 15.37% control — 1023.2 ± 11.1   — a: * P < 0.05, **P < 0.01.

RESULTS: the inhibition effect of integrin-blocking polypeptide I onmigration of HUVECs is shown in Table 1. In contrast with the negativecontrol group, integrin-blocking polypeptide I could inhibit themigration of HUVECs induced by 5% FCS and 1% ECGS; the inhibition effectpresented a certain dose-dependency at medium and low doses. Theinhibition effect of polypeptide I on cell migration presented extremelysignificant difference (**P<0.01) at either high, medium or low dose incontrast with the negative control group; however, the inhibition effectof polypeptide I on cell migration slightly decreased at high dose incontrast with that at medium dose. When the dose of polypeptide I was 16μg/ml, its inhibition effect on cell migration reached the highest41.39%.

The inhibition effect of integrin-blocking polypeptide II on migrationof HUVECs is shown in Table 2. In contrast with the negative controlgroup, integrin-blocking polypeptide II could inhibit the migration ofHUVECs induced by 5% FCS and 1% ECGS; the inhibition effect presented acertain dose-dependency at medium and low doses. The inhibition effectof polypeptide II on cell migration presented extremely significantdifference (**P<0.01) at either high, medium or low dose in contrastwith the negative control group; however, the inhibition effect ofpolypeptide II on cell migration slightly decreased at high dose incontrast with that at medium dose. The inhibition rates at the dose of 4μg/ml, 8 μg/ml and 16 μg/ml were all over 50%, reaching 54.10%, 69.87%and 60.27% respectively. When the dose of polypeptide II was 8 μg/ml,its inhibition effect on cell migration reached the highest 69.87%.

The inhibition effect of integrin-blocking polypeptide III on migrationof HUVECs is shown in Table 3. In contrast with the negative controlgroup, integrin-blocking polypeptide III could inhibit the migration ofHUVECs induced by 5% FCS and 1% ECGS; the inhibition effect presented acertain dose-dependency at medium and low doses. The inhibition effectof polypeptide III on cell migration slightly decreased at high dose incontrast with that at medium dose. The inhibition effect of polypeptideIII at all doses presented extremely significant difference (**P<0.01)on cell migration; the inhibition rate at the dose of 1 μg/ml, 2 μg/mland 4 μg/ml were all over 50%, reaching 76.78%, 62.46% and 52.86%respectively; when the dose of polypeptide III was 1 μg/ml, itsinhibition effect on cell migration reached the highest 76.78%.

Embodiment 4 Test on Integrin-Blocking Polypeptides in InhibitingCapillary Formation of Human Umbilical Vein Endothelial Cells (HUVECs)

Thawing 10 mg/mL matrigel (BD Company, USA) stocked at −20° C. overnightat 4° C., diluting it with HUVEC culture medium at the ratio of 1:1;smearing 30 μl of the solution on a 96-well plate (Greiner Company,USA), placing the plate at a 37° C. incubator for 1 h of aggregation.Digesting the HUVECs with 0.2% ethylene diamine tetraacetic acid (EDTA)when they reached the logarithmic phase; collecting the cells andwashing them with PBS buffer twice, and then resuspending the cells withblank HUVEC culture medium. Counting the cells under a microscope,adjusting the cell concentration to 1×10⁵ cells/ml. Preparing thetesting solution for all groups, and diluting with blank HUVEC culturemedium to 100 μl. Seeding the cells into the 96-well plate, 100 μl foreach well, adding also the testing solution into each well andincubating the cells in 5% CO₂ at 37° C. After 6 h, 12 h, 24 h, 36 h, 48h, 60 h of incubation, randomly choosing 5 FOVs for each dose,photographing and counting the cells; calculating the number ofcapillary structures at different doses and analyzing the inhibitioneffect of polypeptide II and polypeptide III on HUVECs' differentiatinginto capillaries. The inhibition rate of capillary formation wascalculated in accordance with the following formula:

${{inhibition}\mspace{14mu}{rate}\mspace{14mu}{of}\mspace{14mu}{capillary}\mspace{14mu}{formation}\mspace{14mu}(\%)} = {1 - {\frac{N_{test}}{N_{control}} \times 100\;\%}}$

wherein N_(test) is the number of capillary structures in the testgroups while N_(control) is the number of capillary structures in thenegative control group.

Conducting the same experiment three times independently, calculatingmean and standard deviation (mean±SD) of all detected data and analyzingthe data with T-test, wherein *P<0.05 refers to significant differenceand **P<0.01 extremely significant difference.

TABLE 4 inhibition effect of integrin-blocking polypeptide II oncapillary formation of HUVECs time 6 h 12 h number of inhibition numberof inhibition capillary rate (%) of capillary rate (%) of group dosestructures capillary dose structures capillary (n = 5) (μg/ml) (mean ±SD) formation (μg/ml) (mean ± SD) formation polypeptide 0.25 26.0 ± 4.38.45% 0.25 14.0 ± 3.3* 23.08% II 0.5 20.0 ± 0.8** 29.58% 0.5 11.4 ±1.6** 37.36% 1 18.5 ± 5.0** 34.86% 1 10.7 ± 1.2** 40.93% 2  7.2 ± 0.8**74.65% 2  3.5 ± 0.5** 80.77% 4  6.0 ± 1.0** 78.87% 4  3.3 ± 2.5** 81.68%8  8.0 ± 1.4** 71.83% 8  4.3 ± 0.5** 76.19% ES 20 17.0 ± 3.6** 40.14% 2010.3 ± 2.3** 43.22% taxol 10  0.0 ± 0.0** 100.00% 10  0.0 ± 0.0**100.00% control — 28.4 ± 3.0 — — 18.2 ± 1.7 —

TABLE 5 inhibition effect of integrin-blocking polypeptide III oncapillary formation of HUVECs Time 6 h 12 h number of inhibition numberof inhibition capillary rate (%) of capillary rate (%) of group dosestructures capillary dose structures capillary (n = 5) (μg/ml) (mean ±SD) formation (μg/ml) (mean ± SD) formation polypeptide 0.25 26.4 ±1.9** 19.02% 0.25 16.4 ± 1.5** 18.81% III 0.5 20.2 ± 2.3** 37.88% 0.514.6 ± 2.0** 27.39% 1 11.0 ± 1.0** 66.26% 1  8.6 ± 1.5** 57.10% 2 10.6 ±2.8** 67.28% 2  9.0 ± 1.0** 55.45% ES 20 22.0 ± 2.5** 32.52% 20 18.0 ±2.1** 10.89% taxol 10  0.0 ± 0.0**   100% 10  0.0 ± 0.0**   100% control— 32.60 ± 1.34  — — 20.20 ± 1.92  —

RESULTS: The inhibition effect of polypeptide II on differentiation ofHUVECs is shown in Table 4. The differentiation process of HUVECs after6 h-60 h of incubation was observed: the capillary structures started toappear after 6 h of incubation, reached the highest point after 6 h-12 hof incubation, started to decrease after 12 h of incubation and almostcompletely disappeared after 60 h of incubation. The number of capillarystructures in polypeptide II groups (at either high, medium or low dose)was smaller than that in the negative control group, which means thatpolypeptide II presents inhibition effect on HUVECs' differentiatinginto capillaries at either high, medium or low dose; its inhibitionrates at both medium and low doses were over 50%, and they weredose-dependent to some extent. The capillary structures were in minimumnumber when the doses of polypeptide II were 2 μg/ml, 4 μg/ml and 8μg/ml, that is to say, polypeptide II presented the highest inhibitionrate on capillary formation at these doses. After 6 h of incubation, theinhibition rates of polypeptide II at the doses of 2 μg/ml, 4 μg/ml, and8 μg/ml reached 74.65%, 78.87% and 71.83% respectively; after 12 h ofincubation, the inhibition rates of polypeptide II at the doses of 2μg/ml, 4 μg/ml and 8 μg/ml reached 80.77%, 81.68% and 76.19%respectively. After 6 h of incubation, the inhibition effect ofpolypeptide II at the doses of 0.5 μg/ml, 1 μg/ml, 2 μg/ml, 4 μg/ml and8 μg/ml exhibited extremely significant difference in contrast with thenegative control group.

The inhibition effect of polypeptide III on differentiation of HUVECs isshown in Table 5. The differentiation process of HUVECs after 6 h-60 hof incubation was observed: the capillary structures started to appearafter 6 h of incubation, reached the highest point after 6 h-12 h ofincubation, started to decrease after 12 h of incubation and almostcompletely disappeared after 60 h of incubation. The number of capillarystructures in polypeptide III groups (at either high, medium or lowdose) was smaller than that in the negative control group, which meansthat polypeptide III presents inhibition effect on HUVECs'differentiating into capillaries at either high, medium or low dose; itsinhibition rates at both medium and low doses were over 60%, and theywere dose-dependent to some extent. The capillary structures were inminimum number when the doses of polypeptide III were 1 μg/ml and 2μg/ml, that is to say, polypeptide III presented the highest inhibitionrate on capillary formation at these doses. After 6 h of incubation, theinhibition rates of polypeptide III at the doses of 1 μg/ml and 2 μg/mlreached 66.26% and 67.28% respectively. After 12 h of incubation, theinhibition rates of polypeptide III at the doses of 1 μg/ml and 2 μg/mlreached 57.10% and 55.45% respectively. After 6 h of incubation, theinhibition effect of polypeptide III at all does, namely, 0.25 μg/ml,0.5 μg/ml, 1 μg/ml and 2 μg/ml, exhibited extremely significantdifference in contrast with the negative control group.

Embodiment 5 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on TransplantedMelanoma B16F10 in C57BL/6 Black Mice

Taking a certain amount of vigorously growing melanoma tissue, grindingthe tissue under sterile conditions and preparing cell suspension at theconcentration of 1×10⁷ cells/ml, hypodermically inoculating 0.1 ml ofthe cell suspension into the right axillary region of mice. Keepingmeasuring the diameter of the transplanted melanoma with a verniercaliper, and randomly dividing the mice into several groups when thevolume of the tumor reached 100-200 mm³. Observing the dynamic effect ofintegrin-blocking polypeptides on inhibiting the growth of the tumor bymeans of documenting the change of tumor diameters. Measuring the tumordiameter once every other day and recording the body weight of micesimultaneously. Hypodermically injecting polypeptides and other drugsinto the left axillary region of mice from the experimental groupsrespectively while administering only equal quantity of physiologicalsaline to the mice from the negative control group. The total medicationperiod was 14 days, during which cyclophosphamide was administered onceevery other day, taxol once every three days, low-dose polypeptide twicea day and all other drugs once a day. After 14 days of medication,killing the mice and surgically dissecting the tumors and measuring theweight of tumors. The tumor volume (TV) was calculated in accordancewith the following formula:TV=½×a×b ²

wherein a, b refer to the length and width of the tumor respectively.

The relative tumor volume (RTV) can be calculated in accordance with theresults of measurement, using the formula: RTV=V_(t)/V₀, wherein V₀refers to the initial tumor volume measured on the date startingmedication (namely do) while V_(t) the tumor volume obtained throughevery measurement. The anti-tumor activity was evaluated by relativeproliferation rate T/C (%), which was calculated in accordance with thefollowing formula:

${T\text{/}C\mspace{14mu}(\%)} = {\frac{T_{RTV}}{C_{RTV}} \times 100\%}$

wherein T_(RTV) refers to the RTV of test groups; C_(RTV) refers to theRTV of the negative control group.

Conducting the same experiment three times independently, calculatingmean and standard deviation (mean±SD) of all detected data and analyzingthe data with T-test, wherein *P<0.05 refers to significant differenceand **P<0.01 extremely significant difference.

TABLE 6 inhibition effect of polypeptide I on transplanted melanomaB16F10 in C57BL/6 mice dose initial tumor (mg/kg/ weight initial finalfinal tumor weight inhibition group time) (g) number weight (g) number(g) rate control — 16.7 ± 1.0 12 21.9 ± 1.4 12 2.65 ± 1.22 — taxol 1016.5 ± 0.7 10 16.4 ± 2.8 8 0.77 ± 0.62** 70.84% polypeptide 3 17.1 ± 0.810 22.9 ± 1.2 9 1.66 ± 1.35 37.26% I (high) polypeptide 0.75 16.9 ± 1.010 23.6 ± 2.0 9 1.80 ± 0.78 32.17% I (low)

TABLE 7 inhibition effect of polypeptide II on transplanted melanomaB16F10 in C57BL/6 mice dose initial final tumor tumor (mg/kg/ weightinitial weight final weight inhibition group time) (g) number (g) number(g) rate control — 15.8 ± 1.0 12 22.9 ± 1.4 12 3.99 ± 1.03 — taxol 1015.3 ± 0.7 8 16.8 ± 2.8 6 0.98 ± 0.30** 75.49% cyclophosphamide 15 15.2± 0.9 8 17.3 ± 1.5 8 1.40 ± 0.06** 64.95% polypeptide 3 15.7 ± 0.8 821.9 ± 1.2 6 2.36 ± 0.38 40.80% II (high) polypeptide 1.5 15.1 ± 0.5 822.6 ± 0.6 7 2.63 ± 0.69 34.17% II (medium) polypeptide 0.75 15.3 ± 1.08 21.6 ± 2.0 6 1.63 ± 0.53** 59.06% II (low) polypeptide 0.75 15.3 ± 0.98 22.4 ± 1.6 7 1.79 ± 1.03** 55.22% II (low, bid)

TABLE 8 inhibition effect of polypeptide III on transplanted melanomaB16F10 in C57BL/6 mice dose final tumor (mg/kg/ initial weight initialweight final tumor weight inhibition group time) (g) number (g) number(g) rate control — 15.8 ± 1.0 12 22.9 ± 1.4 12 3.99 ± 1.03 — taxol 1015.3 ± 0.7 8 16.8 ± 2.8 6 0.98 ± 0.30** 75.49% cyclophosphamide 15 15.2± 0.9 8 17.3 ± 1.5 8 1.40 ± 0.06** 64.95% polypeptide 0.375 14.7 ± 0.6 822.2 ± 1.8 7 1.47 ± 0.42* 63.07% III (high) polypeptide 0.1875 15.4 ±0.5 8 21.2 ± 1.5 7 1.60 ± 1.09** 59.82% III (medium) polypeptide 0.0937515.5 ± 0.6 8 21.5 ± 0.8 6 1.25 ± 0.47** 68.67% III (low) polypeptideIII0.09375 15.3 ± 0.9 8 22.4 ± 1.6 7 1.23 ± 0.27** 69.21% (low, bid)RESULTS: The inhibition effect of polypeptide I on transplanted melanomaB16F10 in C57BL/6 black mice is shown in Table 6. The taxol group wasadministered with taxol 10 mg/kg/time, and the inhibition rate of taxolon transplanted melanoma B16F10 in C57BL/6 black mice was 70.84%;however, this drug greatly reduced the body weight of animals; theweight of mice from the taxol group was lighter than that from thenegative control group and the polypeptide groups, which means taxolinduces severer toxic and side effects. The inhibition rates ofpolypeptide I at high and low doses on transplanted melanoma B16F10 inC57BL/6 black mice were 37.26% and 32.17% respectively. The resultsabout the inhibition effect of polypeptide I on transplanted melanomaB16F10 in C57BL/6 black mice demonstrated that, in contrast with thenegative control group, polypeptide I presented considerably good effectin inhibiting the growth of the transplanted melanoma B16F10 in C57BL/6black mice; besides, the weight of mice showed no significant change incontrast with the negative control group, and no significant toxic andside effects were observed.

The inhibition effect of polypeptide II on transplanted melanoma B16F10in C57BL/6 black mice is shown in Table 7. The taxol group wasadministered with taxol 10 mg/kg/time, and the inhibition rate of taxolon transplanted melanoma B16F10 in C57BL/6 black mice was 75.49%;however, this drug greatly reduced the body weight of animals; theweight of mice from the taxol group was lighter than that from thecontral group and the polypeptide groups, which means taxol inducesseverer toxic and side effects. The inhibition rates of polypeptide IIat high, medium, low and low twice a day (hereinafter, “low bid”) doseson transplanted melanoma B16F10 in C57BL/6 black mice were 40.80%,34.17%, 59.06% and 55.22% respectively. The tumor volume of mice fromboth the low-dose group and the low-dose bid group exhibited extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the experimental groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide III on transplanted melanoma B16F10in C57BL/6 black mice is shown in Table 8. The inhibition rates ofpolypeptide III at high, medium, low and low-bid doses on transplantedmelanoma B16F10 in C57BL/6 black mice were 63.07%, 59.82%, 68.67% and69.21% respectively. The tumor volume of animals from the high dosepolypeptide III group presented significant difference in contrast withthat from the negative control group; the tumor volumes of animals fromthe medium, low, low-bid polypeptide III groups presented extremelysignificant difference in contrast with that from the negative controlgroup. In contrast with the negative control group, polypeptride IIIpresented most desirable effect in inhibiting growth of transplantedmelanoma B16F10 in C57BL/6 black mice when being administered at 0.09375mg/kg, twice a day; besides, no severe weight change or obvious toxicand side effects were observed on testing animals in contrast with thosefrom the negative control group.

Embodiment 6 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Breast Cancer MDA-MB-231 in Nude Mice

Taking a certain amount of vigorously growing tumor tissue, grinding thetumor tissue under sterile conditions and preparing cell suspension atthe concentration of 1×107 cells/ml; then hypodermicaly inoculating 0.1ml of the cell suspension into the right axillary region of nude mice.Keeping measuring the diameter of the transplanted tumor with a verniercaliper, and randomly dividing the mice into groups when the volume ofthe tumor reached 100-200 mm³. Observing the dynamic effect ofintegrin-blocking polypeptides on inhibiting the growth of the tumor bymeans of documenting the change of tumor diameters. Measuring the tumordiameter once every other day and recording the body weight of micesimultaneously. Intravenously injecting polypeptides to mice from testgroups while administering equal quantity of physiological saline tomice from the negative control group. The total medication period was 14days. Avastin was adopted to set up a positive control group; it wasadministered through the tail vein once every three days while all otherdrugs were administered through the tail vein once a day. Leaving micefor a one-week rest after 14 days' medication, then (21 days aftermedication) killing the mice, surgically dissecting the tumors andmeasuring the weight of tumors. The tumor volume (TV) was calculated inaccordance with the following formula:TV=½×a×b ²

wherein a, b refer to the length and width of the tumor respectively.

The relative tumor volume (RTV) can be calculated in accordance with theresults of measurement, using the formula: RTV=V_(t)/V₀, wherein V₀refers to the initial tumor volume measured on the date startingmedication (namely do) while V_(t) the tumor volume obtained throughevery measurement. The anti-tumor activity was evaluated by relativeproliferation rate T/C (%), which was calculated in accordance with thefollowing formula:

${T\text{/}C\mspace{14mu}(\%)} = {\frac{T_{RTV}}{C_{RTV}} \times 100\%}$

wherein T_(RTV) refers to the RTV of experimental groups; C_(RTV) refersto the RTV of the negative control group.

Conducting the same experiment three times independently, calculatingmean and standard deviation (mean±SD) of all detected data and analyzingthe data with T-test, wherein *P<0.05 refers to significant differenceand **P<0.01 extremely significant difference.

TABLE 9 inhibition effect of polypeptide I on heterotransplanted humanbreast cancer MDA-MB-231 in nude mice dose tumor (mg/kg/ initial weightinitial final weight final tumor weight inhibition group time) (g)number (g) number (g) rate control — 20.19 ± 1.24 12 22.18 ± 1.88 121.19 ± 0.31 — avastin 10 20.50 ± 0.77 10 17.56 ± 1.65 9 0.26 ± 0.08**78.53% endostar(rh- 2.5 19.97 ± 1.19 10 19.67 ± 1.36 10 0.62 ± 0.2147.71% endostatin) polypeptide 3 20.35 ± 0.95 10 19.34 ± 1.13 10 0.56 ±0.10 52.95% I (high) polypeptide 1.5 20.50 ± 1.21 10 20.21 ± 1.97 100.49 ± 0.13** 58.82% I (medium) polypeptide 0.75 20.69 ± 1.20 10 22.28 ±1.75 12 0.58 ± 0.22* 51.26% I (low)

TABLE 10 inhibition effect of polypeptide II on heterotransplanted humanbreast cancer MDA-MB-231 in nude mice dose final tumor (mg/kg/ initialinitial weight final tumor inhibition group time) weight (g) number (g)number weight (g) rate control — 20.11 ± 0.60 12 23.10 ± 0.61 12 1.19 ±0.31 — avastin 10 20.25 ± 0.64 8 21.23 ± 0.47 6 0.26 ± 0.08** 78.53%endostar (rh- 2.5 20.00 ± 0.67 8 22.94 ± 0.64 7 0.62 ± 0.21 47.71%endostatin) polypeptide 3 20.38 ± 0.39 8 23.13 ± 0.67 8 0.43 ± 0.12*63.80% II (high) polypeptide 1.5 20.16 ± 0.45 8 22.86 ± 0.65 8 0.38 ±0.12** 67.82% II (medium) polypeptide 0.75 20.31 ± 0.50 8 23.03 ± 0.65 80.50 ± 0.17* 57.83% II (low)

TABLE 11 inhibition effect of polypeptide III on heterotransplantedhuman breast cancer MDA-MB-231 in nude mice dose final tumor (mg/kg/initial initial weight final tumor inhibition group time) weight (g)number (g) number weight (g) rate control — 20.11 ± 0.60 12 23.10 ± 0.6112 1.19 ± 0.31 — avastin 10 20.25 ± 0.64 8 21.23 ± 0.47 6 0.26 ± 0.08**78.53% endostar (rh- 2.5 20.00 ± 0.67 8 22.94 ± 0.64 7 0.62 ± 0.2147.71% endostatin) polypeptide 0.75 20.09 ± 0.56 8 23.06 ± 0.64 8 0.49 ±0.17* 58.82% III (high) polypeptide 0.375 20.00 ± 0.58 8 22.63 ± 0.57 80.32 ± 0.09** 72.86% III (medium) polypeptide 0.1875 20.03 ± 0.44 823.10 ± 0.42 8 0.45 ± 0.15* 61.91% III (low)RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman breast cancer MDA-MB-231 in nude mice is shown in Table 9. Theinhibition rate of avastin on heterotransplanted human breast cannerMDA-MB-231 in nude mice was 78.53% and the body weight of mice showed noobvious change; the inhibition rates of polypeptide I at high, mediumand low doses on heterotransplanted human breast cancer MDA-MB-231 innude mice were 52.95%, 58.82% and 51.26% respectively. The tumor volumeof mice from the low-dose polypeptide group presented significantdifference in contrast with that from the negative control group; thetumor volume of mice from the medium-dose polypeptide group presentedextremely significant difference in contrast with that from the negativecontrol group. Meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanbreast cancer MDA-MB-231 in nude mice is shown in Table 10. Theinhibition rate of avastin on heterotransplanted human breast cancerMDA-MB-231 in nude mice was 78.53% and the body weight of mice showed noobvious change; the inhibition rates of polypeptide II at high, mediumand low doses on heterotransplanted human breast cancer MDA-MB-231 innude mice were 63.80%, 67.82% and 57.83% respectively. The tumor volumeof mice from both the high-dose group and the low-dose group presentedsignificant difference in contrast with that from the negative controlgroup; the tumor volume of mice from the medium-dose group presentedextremely significant difference in contrast with that from the negativecontrol group; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide III on heterotransplanted humanbreast cancer MDA-MB-231 in nude mice is shown in Table 11. Theinhibition rate of avastin on heterotransplanted human breast cancerMDA-MB-231 in nude mice was 68.95% and the body weight of mice showed noobvious change; the inhibition rates of polypeptide III at high, mediumand low doses on heterotransplanted human breast cancer MDA-MB-231 innude mice were 58.82%, 72.86% and 61.91% respectively. The tumor volumeof mice from both the high-dose group and the low-dose group presentedsignificant difference in contrast with that from the negative controlgroup; the tumor volume of mice from the medium-dose group presentedextremely significant difference in contrast with that from the negativecontrol group; meanwhile, animals from the experimental groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

Embodiment 7 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Gastric Cancer MGC-803 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Oxaliplatin and xeloda were adopted toset up the positive control group, administering oxaliplatin once everyfour days through tail vein injection and xeloda once the other daythrough oral gavage; drugs of all other groups were administered ondaily basis through tail vein injection.

TABLE 12 inhibition effect of polypeptide I on heterotransplanted humangastric cancer MGC-803 in nude mice dose initial final tumor tumor(mg/kg/ weight initial weight final weight inhibition group time) (g)number (g) number (g) rate control — 20.00 ± 0.52 12 23.33 ± 0.44 120.78 ± 0.22 — oxaliplatin + oxaliplatin 20.09 ± 0.70 8 20.47 ± 0.70 60.32 ± 0.13* 51.76% xeloda 3.3 mg/kg xeloda 35 mg/kg polypeptide 3 20.18± 0.61 8 23.23 ± 0.67 7 0.48 ± 0.13 38.28% I (high) polypeptide 1.520.02 ± 0.52 8 22.66 ± 0.61 8 0.42 ± 0.10 38.46% I (medium) polypeptide0.75 20.14 ± 0.52 8 22.98 ± 0.60 8 0.50 ± 0.13 35.90% I (low)

TABLE 13 inhibition effect of polypeptide II on heterotransplanted humangastric cancer MGC-803 in nude mice dose final tumor tumor (mg/kg/initial initial weight final weight inhibition group time) weight (g)number (g) number (g) rate control — 20.29 ± 1.29 12 22.08 ± 1.88 120.78 ± 0.22 — oxaliplatin + oxaliplatin 20.20 ± 0.75 10 17.50 ± 1.95 90.32 ± 0.13* 51.76% xeloda 3.3 mg/kg xeloda 35 mg/kg polypeptide 3 19.95± 1.21 10 19.60 ± 1.26 10 0.48 ± 0.13 38.28% II (high) polypeptide 1.520.15 ± 0.97 10 19.67 ± 1.41 10 0.16 ± 0.10** 79.72% II (medium)polypeptide 0.75 20.00 ± 1.22 10 20.40 ± 1.26 10 0.23 ± 0.13** 70.67% II(low)

TABLE 14 inhibition effect of polypeptide III on heterotransplantedhuman gastric cancer MGC-803 in nude mice dose final Tumor tumor (mg/kg/initial weight initial weight final weight inhibition group time) (g)number (g) number (g) rate control — 20.29 ± 1.29 12 22.08 ± 1.88 120.78 ± 0.22 — oxaliplatin + oxaliplatin 20.20 ± 0.75 10 17.50 ± 1.95 90.32 ± 0.13* 51.76% xeloda 3.3 mg/kg xeloda 35 mg/kg polypeptide 0.7519.75 ± 0.65 10 20.88 ± 0.85 10 0.33 ± 0.09 57.65% III (high)polypeptide 0.375 19.63 ± 0.75 10 20.13 ± 1.03 10 0.27 ± 0.06* 66.03%III (medium) polypeptide 0.1875 20.25 ± 0.65 10 22.25 ± 1.71 10 0.23 ±0.05** 70.08% III (low)RESULTS: The inhibition effect of polypeptide I on heterotransplantedhuman gastric cancer MGC-803 in nude mice is shown in Table 12. Theinhibition rate of the oxaliplatin+xeloda group on heterotransplantedhuman gastric cancer MGC-803 in nude mice was 51.76%; however, thiscombination chemotherapy greatly reduced the body weight of animals;mice treated in this way showed lighter body weight and more apparenttoxic and side effects than those from the negative control group. Theinhibition rates of polypeptide I at high, medium and low doses onheterotransplanted human gastric cancer MGC-803 in nude mice were38.28%, 38.46% and 35.90% respectively; meanwhile, animals from thepolypeptide groups showed no significant change in body weight, and noobvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide II on heterotransplanted humangastric cancer MGC-803 in nude mice is shown in Table 13. The inhibitionrate of the oxaliplatin+xeloda group on heterotransplanted human gastriccancer MGC-803 in nude mice was 51.76%; however, this combinationchemotherapy greatly reduced the body weight of animals; mice treated inthis way showed lighter body weight and more apparent toxic and sideeffects than those from the negative control group. The inhibition ratesof polypeptide II at high, medium and low doses on heterotransplantedhuman gastric cancer MGC-803 in nude mice were 38.28%, 79.72% and 70.67%respectively. The tumor volume of mice from both the medium-dose groupand the low-dose group exhibited extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide III on heterotransplanted humangastric cancer MGC-803 in nude mice is shown in Table 14. The inhibitionrate of the oxaliplatin+xeloda group on heterotransplanted human gastriccancer MGC-803 in nude mice was 51.76%; however, this combinationchemotherapy greatly reduced the body weight of animals; mice treated inthis way showed lighter body weight and more apparent toxic and sideeffects than those from the negative control group. The inhibition ratesof polypeptide III at high, medium and low doses on heterotransplantedhuman gastric cancer MGC-803 in nude mice were 57.65%, 66.03% and 70.08%respectively. The tumor volume of mice from the medium-dose grouppresented significant difference in contrast with that from the negativecontrol group; the tumor volume of mice from the low-dose grouppresented extremely significant difference in contrast with that fromthe negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

Embodiment 8 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Lung Cancer H460 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Taxol used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 15 inhibition effect of polypeptide I on heterotransplanted humanlung cancer H460 in nude mice dose initial final tumor (mg/kg/ weightinitial weight final tumor inhibition group time) (g) number (g) numberweight (g) rate control — 19.99 ± 0.72 12 23.13 ± 0.51 12 0.88 ± 0.23 —taxol 10 20.13 ± 0.57 8 17.80 ± 0.63 7 0.28 ± 0.07** 68.21% polypeptideI 3 19.94 ± 0.65 8 22.96 ± 0.69 8 0.47 ± 0.17* 46.60% (high) polypeptideI 1.5 20.05 ± 0.52 8 22.93 ± 0.51 8 0.40 ± 0.05** 54.54% (medium)polypeptide I 0.75 19.91 ± 0.57 8 23.13 ± 0.58 8 0.51 ± 0.17* 42.05%(low)

TABLE 16 inhibition effect of polypeptide II on heterotransplanted humanlung cancer H460 in nude mice dose tumor (mg/kg/ initial weight initialfinal weight final tumor inhibition group time) (g) number (g) numberweight (g) rate control — 20.13 ± 0.61 12 23.07 ± 0.53 12 0.88 ± 0.23 —taxol 10 20.05 ± 0.68 8 18.09 ± 0.55 7 0.28 ± 0.07** 68.21% polypeptide3 20.21 ± 0.57 8 22.59 ± 0.53 8 0.37 ± 0.17* 57.68% II (high)polypeptide 1.5 20.06 ± 0.47 8 23.26 ± 0.40 8 0.30 ± 0.05** 65.37% II(medium) polypeptide 0.75 20.02 ± 0.51 8 22.87 ± 0.40 8 0.41 ± 0.17*53.49% II (low)

TABLE 17 inhibition effect of polypeptide III on heterotransplantedhuman lung cancer H460 in nude mice dose tumor (mg/kg/ initial initialfinal weight final tumor weight inhibition group time) weight (g) number(g) number (g) rate control — 20.13 ± 0.61 12 23.07 ± 0.53 12 0.88 ±0.23 — taxol 10 20.05 ± 0.68 8 18.09 ± 0.55 7 0.28 ± 0.07** 68.21%polypeptide 0.75 20.14 ± 0.64 8 23.14 ± 0.51 8 0.28 ± 0.11** 68.05% III(high) polypeptide 0.375 19.89 ± 0.62 8 23.12 ± 0.53 8 0.23 ± 0.06**74.42% III (medium) polypeptide 0.1875 20.36 ± 0.68 8 23.15 ± 0.49 80.27 ± 0.05** 69.23% III (low)RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman lung cancer H460 in nude mice is shown in Table 15. The inhibitionrate of the taxol group on heterotransplanted human lung cancer H460 innude mice was 68.21%, however, this chemotherapy greatly reduced thebody weight of animals; mice treated in this way showed lighter bodyweight and more apparent toxic and side effects than those from thenegative control group and the polypeptide groups. The inhibition ratesof polypeptide I at high, medium and low doses on heterotransplantedhuman lung cancer H460 in nude mice were 46.60%, 54.54% and 42.05%respectively. The tumor volume of mice from both the high-dose group andthe low-dose group presented significant difference in contrast withthat from the negative control group; the tumor volume of mice from themedium-dose group presented extremely significant difference in contrastwith that from the negative control group; meanwhile, animals from thepolypeptide groups showed no significant change in body weight, and noobvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide II on heterotransplanted human lungcancer H460 in nude mice is shown in Table 16. The inhibition rate ofthe taxol group on heterotransplanted human lung cancer H460 in nudemice was 68.21%, however, this chemotherapy greatly reduced the bodyweight of animals; mice treated in this way showed lighter body weightand more apparent toxic and side effects than those from the negativecontrol group and the polypeptide groups. The inhibition rates ofpolypeptide II at high, medium and low doses on heterotransplanted humanlung cancer H460 in nude mice were 57.68%, 65.37% and 53.49%respectively. The tumor volume of mice from both the high-dose group andthe low-dose group presented significant difference in contrast withthat from the negative control group; the tumor volume of mice from themedium-dose group presented extremely significant difference in contrastwith that from the negative control group; meanwhile, animals from thepolypeptide groups showed no significant change in body weight, and noobvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide III on heterotransplanted humanlung cancer H460 in nude mice is shown in Table 17. The inhibition rateof the taxol group on heterotransplanted human lung cancer H460 in nudemice was 68.21%, however, this chemotherapy greatly reduced the bodyweight of animals; mice treated in this way showed lighter body weightand more apparent toxic and side effects than those from the negativecontrol group and the polypeptide groups. The inhibition rates ofpolypeptide III at high, medium and low doses on heterotransplantedhuman lung cancer H460 in nude mice were 68.05%, 74.42% and 69.23%respectively. All polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, presented extremelysignificant difference in contrast with the negative control group;meanwhile, animals from the polypeptide groups showed no significantchange in body weight, and no obvious toxic and side effects wereobserved in contrast with the negative control group.

Embodiment 9 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Liver Cancer SMMC-7721 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Taxol used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 18 inhibition effect of polypeptide I on heterotransplanted humanliver cancer SMMC-7721 in nude mice dose (mg/kg/ initial initial finalweight final tumor tumor group time) weight (g) number (g) number weight(g) inhibition rate control — 19.77 ± 0.61 12 23.04 ± 0.61 12 1.27 ±0.23 — taxol 10 20.11 ± 0.52 8 17.22 ± 0.51 7 0.28 ± 0.05** 78.10%endostar (rh- 2.5 19.83 ± 0.49 8 23.04 ± 0.68 8 0.79 ± 0.29 36.96%endostatin) polypeptide 3 20.18 ± 0.62 8 22.84 ± 0.55 8 0.55 ± 0.12*56.70% I (high) polypeptide 1.5 20.23 ± 0.67 8 22.99 ± 0.55 8 0.47 ±0.14** 63.00% I (medium) polypeptide 0.75 19.93 ± 0.54 8 23.17 ± 0.63 80.53 ± 0.04* 58.26% I (low)

TABLE 19 inhibition effect of polypeptide II on heterotransplanted humanliver cancer SMMC-7721 in nude mice dose tumor (mg/kg/ initial weightinitial final final weight tumor group time) (g) number weight (g)number (g) inhibition rate control — 19.83 ± 0.61 12 23.26 ± 0.55 121.27 ± 0.23 — taxol 10 19.81 ± 0.54 8 16.90 ± 0.51 7 0.28 ± 0.05**78.10% endostar (rh- 2.5 19.73 ± 0.50 8 23.02 ± 0.62 8 0.79 ± 0.2936.96% endostatin) polypeptide 3 19.87 ± 0.66 8 22.90 ± 0.59 8 0.39 ±0.05** 68.75% II (high) polypeptide 1.5 20.15 ± 0.56 8 22.93 ± 0.60 80.31 ± 0.07** 75.12% II (medium) polypeptide 0.75 20.10 ± 0.39 8 23.21 ±0.60 8 0.36 ± 0.05** 71.54% II (low)

TABLE 20 inhibition effect of polypeptide III on heterotransplantedhuman liver cancer SMMC-7721 in nude mice dose (mg/kg/ initial initialfinal weight final tumor tumor group time) weight (g) number (g) numberweight (g) inhibition rate control — 19.83 ± 0.61 12 23.26 ± 0.55 121.27 ± 0.23 — taxol 10 19.81 ± 0.54 8 16.90 ± 0.51 7 0.28 ± 0.05**78.10% endostar (rh- 2.5 19.73 ± 0.50 8 23.02 ± 0.62 8 0.79 ± 0.2936.96% endostatin) polypeptide 0.75 19.89 ± 0.72 8 22.63 ± 0.39 8 0.28 ±0.03** 77.55% III (high) polypeptide 0.375 19.97 ± 0.50 8 23.25 ± 0.54 80.22 ± 0.03** 82.55% III (medium) polypeptide 0.1875 19.91 ± 0.46 822.70 ± 0.57 8 0.35 ± 0.04** 71.85% III (low)RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman liver cancer SMMC-7721 in nude mice is shown in Table 18. Theinhibition rate of the taxol group on heterotransplanted human livercancer SMMC-7721 in nude mice was 78.10%, however, this chemotherapygreatly reduced the body weight of animals; mice treated in this wayshowed lighter body weight and more apparent toxic and side effects thanthose from the negative control group and the polypeptide groups. Theinhibition rates of polypeptide I at high, medium and low doses onheterotransplanted human liver cancer SMMC-7721 in nude mice were 56.70,63.00% and 58.26% respectively. The tumor volume of mice from both thehigh-dose group and the low-dose group presented significant differencein contrast with that from the negative control group; the tumor volumeof mice from the medium-dose group presented extremely significantdifference in contrast with that from the negative control group;meanwhile, animals from the polypeptide groups showed no significantchange in body weight, and no obvious toxic and side effects wereobserved in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanliver cancer SMMC-7721 in nude mice is shown in Table 19. The inhibitionrate of the taxol group on heterotransplanted human liver cancerSMMC-7721 in nude mice was 78.10%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide II at high, medium and low doses onheterotransplanted human liver cancer SMMC-7721 in nude mice were68.75%, 75.12% and 71.54% respectively. All polypeptide groups,including the high-dose group, the medium-dose group and the low-dosegroup, presented extremely significant difference in contrast with thenegative control group; meanwhile, animals from the polypeptide groupsshowed no significant change in body weight, and no obvious toxic andside effects were observed in contrast with the negative control group.

The inhibition effect of polypeptide III on heterotransplanted humanliver cancer SMMC-7721 in nude mice is shown in Table 20. The inhibitionrate of the taxol group on heterotransplanted human liver cancerSMMC-7721 in nude mice was 78.10%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide III at high, medium and low doses onheterotransplanted human liver cancer SMMC-7721 in nude mice were77.55%, 82.55% and 71.85% respectively. All polypeptide groups,including the high-dose group, the medium-dose group and the low-dosegroup, presented extremely significant difference in contrast with thenegative control group; meanwhile, animals from the polypeptide groupsshowed no significant change in body weight, and no obvious toxic andside effects were observed in contrast with the negative control group.

Embodiment 10 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Cervical Cancer HeLa in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Cisplatin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 21 inhibition effect of polypeptide I on heterotransplanted humancervical cancer HeLa in nude mice dose initial tumor (mg/kg/ weightinitial final final weight tumor group time) (g) number weight (g)number (g) inhibition rate control — 20.00 ± 0.52 12 23.33 ± 0.44 121.40 ± 0.37 — cisplatin 10 20.09 ± 0.70 8 20.47 ± 0.70 6 0.38 ± 0.10**73.13% endostar (rh- 2.5 20.18 ± 0.61 8 23.23 ± 0.67 7 0.80 ± 0.2043.08% endostatin) polypeptide 3 20.07 ± 0.53 8 23.18 ± 0.51 8 0.52 ±0.05** 62.85% I (high) polypeptide 1.5 20.17 ± 0.48 8 22.96 ± 0.57 80.41 ± 0.07** 70.71% I (medium) polypeptide 0.75 19.62 ± 0.52 8 22.94 ±0.46 8 0.49 ± 0.05** 65.00% I (low)

TABLE 22 inhibition effect of polypeptide II on heterotransplanted humancervical cancer HeLa in nude mice dose tumor (mg/kg/ initial initialfinal final weight tumor group time) weight (g) number weight (g) number(g) inhibition rate control — 20.05 ± 0.58 12 23.12 ± 0.57 12 1.40 ±0.37 — cisplatin 10 20.16 ± 0.54 8 17.28 ± 0.56 7 0.38 ± 0.10** 73.13%endostar (rh- 2.5 19.84 ± 0.55 8 23.14 ± 0.54 8 0.80 ± 0.20 43.08%endostatin) polypeptide 3 19.92 ± 0.75 8 22.99 ± 0.52 8 0.62 ± 0.18*55.82% II (high) polypeptide 1.5 20.12 ± 0.63 8 22.88 ± 0.55 8 0.45 ±0.11** 68.19% II (medium) polypeptide 0.75 20.03 ± 0.57 8 23.14 ± 0.55 80.50 ± 0.12** 64.45% II (low)

TABLE 23 inhibition effect of polypeptide III on heterotransplantedhuman cervical cancer HeLa in nude mice dose (mg/kg/ initial weightinitial final weight final tumor tumor group time) (g) number (g) numberweight (g) inhibition rate control — 20.05 ± 0.58 12 23.12 ± 0.57 121.40 ± 0.37 — cisplatin 10 20.16 ± 0.54 8 17.28 ± 0.56 7 0.38 ± 0.10**73.13% endostar (rh- 2.5 19.84 ± 0.55 8 23.14 ± 0.54 8 0.80 ± 0.2043.08% endostatin) polypeptide 0.75 19.76 ± 0.43 8 22.88 ± 0.66 8 0.50 ±0.15** 64.35% III (high) Polypeptide 0.375 20.19 ± 0.60 8 23.17 ± 0.58 80.39 ± 0.08** 72.41% III (medium) polypeptide 0.1875 19.98 ± 0.65 823.10 ± 0.56 8 0.44 ± 0.11** 68.68% III (low)RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman cervical cancer HeLa in nude mice is shown in Table 21. Theinhibition rate of the cisplatin group on heterotransplanted humancervical cancer HeLa in nude mice was 73.13%, however, this chemotherapygreatly reduced the body weight of animals; mice treated in this wayshowed lighter body weight and more apparent toxic and side effects thanthose from the negative control group and the polypeptide groups. Theinhibition rates of polypeptide I at high, medium and low doses onheterotransplanted human cervical cancer HeLa in nude mice were 62.85%,70.71% and 65.00% respectively. The tumor volume of mice from allpolypeptide groups, including the high-dose group, the medium-dose groupand the low-dose group, exhibited extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide II on heterotransplanted humancervical cancer HeLa in nude mice is shown in Table 22. The inhibitionrate of the cisplatin group on heterotransplanted human cervical cancerHeLa in nude mice was 73.13%, however, this chemotherapy greatly reducedthe body weight of animals; mice treated in this way showed lighter bodyweight and more apparent toxic and side effects than those from thenegative control group and the polypeptide groups. The inhibition ratesof polypeptide II at high, medium and low doses on heterotransplantedhuman cervical cancer HeLa in nude mice were 55.82%, 68.19% and 64.45%respectively. The tumor volume of mice from all polypeptide groups,including the high-dose group, the medium-dose group and the low-dosegroup, exhibited extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

The inhibition effect of polypeptide III on heterotransplanted humancervical cancer HeLa in nude mice is shown in Table 23. The inhibitionrate of the cisplatin group on heterotransplanted human cervical cancerHeLa in nude mice was 73.13%, however, this chemotherapy greatly reducedthe body weight of animals; mice treated in this way showed lighter bodyweight and more apparent toxic and side effects than those from thenegative control group and the polypeptide groups. The inhibition ratesof polypeptide III at high, medium and low doses on heterotransplantedhuman cervical cancer HeLa in nude mice were 64.35%, 72.41% and 68.68%respectively. The tumor volume of mice from all polypeptide groups,including the high-dose group, the medium-dose group and the low-dosegroup, exhibited extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

Embodiment 11 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Endometrial Cancer HHUA in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Taxol used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 24 inhibition effect of polypeptide I on heterotransplanted humanendometrial cancer HHUA in nude mice dose tumor (mg/kg/ initial initialfinal weight final weight tumor group time) weight (g) number (g) number(g) inhibition rate control — 20.09 ± 0.66 12 23.01 ± 0.48 12 1.14 ±0.35 — taxol 10 20.94 ± 0.58 8 18.88 ± 0.68 7 0.23 ± 0.07** 79.82%endostar (rh- 2.5 20.88 ± 0.79 8 22.89 ± 0.51 8 0.65 ± 0.15 43.00%endostatin) polypeptide 3 19.82 ± 0.60 8 23.14 ± 0.48 8 0.60 ± 0.1447.36% I (high) polypeptide 1.5 19.96 ± 0.58 8 22.93 ± 0.56 8 0.51 ±0.10* 55.30% I (medium) polypeptide 0.75 19.87 ± 0.58 8 22.81 ± 0.60 80.52 ± 0.12* 54.39% I (low)

TABLE 25 inhibition effect of polypeptide II on heterotransplanted humanendometrial cancer HHUA in nude mice dose (mg/kg/ initial weight initialfinal weight final tumor tumor inhibition group time) (g) number (g)number weight (g) rate control — 20.09 ± 0.66 12 23.01 ± 0.48 12 1.14 ±0.35 — taxol 10 20.94 ± 0.58 8 18.88 ± 0.68 7 0.23 ± 0.07** 79.82%endostar (rh- 2.5 20.88 ± 0.79 8 22.89 ± 0.51 8 0.65 ± 0.15 43.00%endostatin) polypeptide 3 20.08 ± 0.59 8 23.04 ± 0.55 8 0.46 ± 0.11**59.65% II (high) polypeptide 1.5 19.70 ± 0.52 8 22.95 ± 0.46 8 0.37 ±0.07** 67.54% II (medium) polypeptide 0.75 20.28 ± 0.61 8 22.93 ± 0.46 80.41 ± 0.11** 64.03% II (low)

TABLE 26 inhibition effect of polypeptide III on heterotransplantedhuman endometrial cancer HHUA in nude mice dose (mg/kg/ initial initialfinal final tumor tumor group time) weight (g) number weight (g) numberweight (g) inhibition rate control — 20.09 ± 0.66 12 23.01 ± 0.48 121.14 ± 0.35 — taxol 10 20.94 ± 0.58 8 18.88 ± 0.68 7 0.23 ± 0.07**79.82% endostar (rh- 2.5 19.88 ± 0.79 8 22.89 ± 0.51 8 0.65 ± 0.1543.00% endostatin) polypeptide 0.75 19.89 ± 0.53 8 23.07 ± 0.56 8 0.38 ±0.10** 66.67% III (high) polypeptide 0.375 20.31 ± 0.51 8 23.18 ± 0.57 80.30 ± 0.06** 73.21% III (medium) polypeptide 0.1875 19.74 ± 0.55 822.92 ± 0.57 8 0.33 ± 0.07** 70.53% III (low)

RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman endometrial cancer HHUA in nude mice is shown in Table 24. Theinhibition rate of the taxol group on heterotransplanted humanendometrial cancer HHUA in nude mice was 79.82%, however, thischemotherapy greatly reduced the body weight of animals; mice treated inthis way showed lighter body weight and more apparent toxic and sideeffects than those from the negative control group and the polypeptidegroups. The inhibition rates of polypeptide I at high, medium and lowdoses on heterotransplanted human endometrial cancer HHUA in nude micewere 47.36%, 55.30% and 54.39% respectively. The tumor volume of micefrom both the medium-dose group and the low-dose group exhibitedsignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanendometrial cancer HHUA in nude mice is shown in Table 25. Theinhibition rate of the taxol group on heterotransplanted humanendometrial cancer HHUA in nude mice was 79.82%, however, thischemotherapy greatly reduced the body weight of animals; mice treated inthis way showed lighter body weight and more apparent toxic and sideeffects than tat from the negative control group and the polypeptidegroups. The inhibition rates of polypeptide II at high, medium and lowdoses on heterotransplanted human endometrial cancer HHUA in nude micewere 59.65%, 67.54% and 64.03% respectively. The tumor volume of micefrom all polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide III on heterotransplanted humanendometrial cancer HHUA in nude mice is shown in Table 26. Theinhibition rate of the taxol group on heterotransplanted humanendometrial cancer HHUA in nude mice was 73.13%, however, thischemotherapy greatly reduced the body weight of animals; mice treated inthis way showed lighter body weight and more apparent toxic and sideeffects than those from the negative control group and the polypeptidegroups. The inhibition rates of polypeptide III at high, medium and lowdoses on heterotransplanted human endometrial cancer HHUA in nude micewere 66.67%, 73.21% and 70.53% respectively. The tumor volume of micefrom all polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

Embodiment 12 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Prostate Cancer DU-145 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Cisplatin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 27 inhibition effect of polypeptide I on heterotransplanted humanprostate cancer DU-145 in nude mice dose tumor (mg/kg/ initial initialfinal weight final weight tumor group time) weight (g) number (g) number(g) inhibition rate control — 19.77 ± 0.61 12 23.04 ± 0.61 12 1.43 ±0.34 — cisplatin 10 20.11 ± 0.52 8 17.22 ± 0.51 7 0.37 ± 0.10** 73.84%endostar (rh- 2.5 19.83 ± 0.49 8 23.04 ± 0.68 8 0.86 ± 0.16 38.46%endostatin) polypeptide 3 19.88 ± 0.58 8 22.99 ± 0.37 8 0.48 ± 0.10**66.43% I (high) polypeptide 1.5 19.97 ± 0.66 8 23.10 ± 0.61 8 0.40 ±0.16** 72.02% I (medium) polypeptide 0.75 20.07 ± 0.54 8 22.85 ± 0.61 80.46 ± 0.14** 67.83% I (low)

TABLE 28 inhibition effect of polypeptide II on heterotransplanted humanprostate cancer DU-145 in nude mice dose tumor (mg/kg/ initial initialfinal final weight tumor inhibition group time) weight (g) number weight(g) number (g) rate control — 19.77 ± 0.61 12 23.04 ± 0.61 12 1.43 ±0.34 — cisplatin 10 20.11 ± 0.52 8 17.22 ± 0.51 7 0.37 ± 0.10** 73.84%endostar (rh- 2.5 19.83 ± 0.49 8 23.04 ± 0.68 8 0.86 ± 0.16 38.46%endostatin) polypeptide 3 19.63 ± 0.49 8 22.99 ± 0.55 8 0.65 ± 0.14*54.25% II (high) polypeptide 1.5 20.08 ± 0.46 8 23.04 ± 0.48 8 0.46 ±0.10** 67.83% II (medium) polypeptide 0.75 20.31 ± 0.60 8 23.10 ± 0.48 80.53 ± 0.12** 62.92% II (low)

TABLE 29 inhibition effect of polypeptide III on heterotransplantedhuman prostate cancer DU-145 in nude mice dose tumor (mg/kg/ initialweight initial final weight final weight tumor group time) (g) number(g) number (g) inhibition rate control 10 19.77 ± 0.61 12 23.04 ± 0.6112 1.43 ± 0.34 — cisplatin 5 20.11 ± 0.52 8 17.22 ± 0.51 7 0.37 ± 0.10**73.84% endostar (rh- 2.5 19.83 ± 0.49 8 23.04 ± 0.68 8 0.86 ± 0.1638.46% endostatin) polypeptide 0.75 20.18 ± 0.62 8 22.84 ± 0.55 8 0.56 ±0.14** 60.73% III (high) polypeptide 0.375 20.23 ± 0.67 8 22.99 ± 0.55 80.43 ± 0.13** 69.90% III (medium) polypeptide 0.1875 19.93 ± 0.54 823.17 ± 0.63 8 0.51 ± 0.15** 64.08% III (low)RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman prostate cancer DU-145 in nude mice is shown in Table 27. Theinhibition rate of the cisplatin group on heterotransplanted humanprostate cancer DU-145 in nude mice was 73.84%, however, thischemotherapy greatly reduced the body weight of animals; mice treated inthis way showed lighter body weight and more apparent toxic and sideeffects than those from the negative control group and the polypeptidegroups. The inhibition rates of polypeptide I at high, medium and lowdoses on heterotransplanted human prostate cancer DU-145 in nude micewere 66.43%, 72.02% and 67.83% respectively. The tumor volume of micefrom all polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanprostate cancer DU-145 in nude mice is shown in Table 28. The inhibitionrate of the cisplatin group on heterotransplanted human prostate cancerDU-145 in nude mice was 73.84%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide II at high, medium and low doses onheterotransplanted human prostate cancer DU-145 in nude mice were54.25%, 67.83% and 62.92% respectively. The tumor volume of mice fromthe high-dose group presented significant difference in contrast withthat from the negative control group; the tumor volume of mice from boththe medium-dose group and the low-dose group presented extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide III on heterotransplanted humanprostate cancer DU-145 in nude mice is shown in Table 29. The inhibitionrate of the cisplatin group on heterotransplanted human prostate cancerDU-145 in nude mice was 73.84%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide III at high, medium and low doses onheterotransplanted human prostate cancer DU-145 in nude mice were60.73%, 69.90% and 64.08% respectively. The tumor volume of mice fromall polypeptide groups, including the high-dose group, the medium-dosegroup and the low-dose group, exhibited extremely significant differencein contrast with that from the negative control group; meanwhile,animals from the polypeptide groups showed no significant change in bodyweight, and no obvious toxic and side effects were observed in contrastwith the negative control group.

Embodiment 13 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Testicular Cancer 5637 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. 5-fluorouracil (5-FU) used in thepositive control group was administered once every 3 days through tailvein injection, while drugs of all other groups were administered ondaily basis through tail vein injection.

TABLE 30 inhibition effect of polypeptide I on heterotransplanted humantesticular cancer 5637 in nude mice dose (mg/kg/ initial weight initialfinal weight final tumor tumor group time) (g) number (g) number weight(g) inhibition rate control — 20.09 ± 0.65 12 23.11 ± 0.61 12 1.26 ±0.29 — 5-Fu 10 19.90 ± 0.48 8 17.03 ± 0.53 7 0.28 ± 0.06** 77.80%endostar (rh- 2.5 20.00 ± 0.70 8 22.98 ± 0.72 8 0.76 ± 0.21 39.49%endostatin) polypeptide 3 19.83 ± 0.49 8 23.04 ± 0.68 8 0.57 ± 0.11*54.76% I (high) polypeptide 1.5 19.63 ± 0.49 8 22.99 ± 0.55 8 0.46 ±0.10** 63.49% I (medium) polypeptide 0.75 20.08 ± 0.46 8 23.04 ± 0.48 80.55 ± 0.11* 56.34% I (low)

TABLE 31 inhibition effect of polypeptide II on heterotransplanted humantesticular cancer 5637 in nude mice dose (mg/kg/ initial weight initialfinal final tumor tumor group time) (g) number weight (g) number weight(g) inhibition rate control — 20.09 ± 0.65 12 23.11 ± 0.61 12 1.26 ±0.29 — 5-Fu 10 19.90 ± 0.48 8 17.03 ± 0.53 7 0.28 ± 0.06** 77.80%endostar (rh- 2.5 20.00 ± 0.70 8 22.98 ± 0.72 8 0.76 ± 0.21 39.49%endostatin) polypeptide 3 20.03 ± 0.61 8 23.16 ± 0.51 8 0.60 ± 0.16*52.49% II (high) polypeptide 1.5 20.05 ± 0.58 8 22.96 ± 0.59 8 0.45 ±0.10** 64.32% II (medium) polypeptide 0.75 19.97 ± 0.62 8 23.09 ± 0.59 80.49 ± 0.11** 60.96% II (low)

TABLE 32 inhibition effect of polypeptide III on heterotransplantedhuman testicular cancer 5637 in nude mice dose (mg/kg/ initial initialfinal weight final tumor tumor group time) weight (g) number (g) numberweight (g) inhibition rate control — 20.09 ± 0.65 12 23.11 ± 0.61 121.26 ± 0.29 — 5-Fu 10 19.90 ± 0.48 8 17.03 ± 0.53 7 0.28 ± 0.06** 77.80%endostar (rh- 2.5 20.00 ± 0.70 8 22.98 ± 0.72 8 0.76 ± 0.21 39.49%endostatin) polypeptide 0.75 19.96 ± 0.57 8 23.12 ± 0.73 8 0.50 ± 0.10**60.51% III (high) polypeptide 0.375 20.03 ± 0.60 8 23.35 ± 0.50 8 0.44 ±0.12** 65.11% III (medium) polypeptide 0.1875 19.89 ± 0.57 8 23.02 ±0.64 8 0.47 ± 0.12** 62.63% III (low)RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman testicular cancer 5637 in nude mice is shown in Table 30. Theinhibition rate of the 5-FU group on heterotransplanted human testicularcancer 5637 in nude mice was 77.80%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide I at high, medium and low doses onheterotransplanted human testicular cancer 5637 in nude mice were54.76%, 63.49% and 56.34% respectively. The tumor volume of mice fromboth the high-dose group and low-dose group presented significantdifference in contrast with that from the negative control group; thetumor volume of mice from the medium-dose group presented extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humantesticular cancer 5637 in nude mice is shown in Table 31. The inhibitionrate of the 5-FU group on heterotransplanted human testicular cancer5637 in nude mice was 77.80%, however, this chemotherapy greatly reducedthe body weight of animals; mice treated in this way showed lighter bodyweight and more apparent toxic and side effects than those from thenegative control group and the polypeptide groups. The inhibition ratesof polypeptide II at high, medium and low doses on heterotransplantedhuman testicular cancer 5637 in nude mice were 52.49%, 64.32% and 60.96%respectively. The tumor volume of mice from the high-dose grouppresented significant difference in contrast with that from the negativecontrol group; the tumor volume of mice from both the medium-dose groupand the low-dose group presented extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide III on heterotransplanted humantesticular cancer 5637 in nude mice is shown in Table 32. The inhibitionrate of the 5-FU group on heterotransplanted human testicular cancer5637 in nude mice was 73.84%, however, this chemotherapy greatly reducedthe body weight of animals; mice treated in this way showed lighter bodyweight and more apparent toxic and side effects than those from thenegative control group and the polypeptide groups. The inhibition ratesof polypeptide III at high, medium and low doses on heterotransplantedhuman testicular cancer 5637 in nude mice were 60.51%, 65.11% and 62.63%respectively. The tumor volume of mice from all polypeptide groups,including the high-dose group, the medium-dose group and the low-dosegroup, exhibited extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

Embodiment 14 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Gallbladder Cancer GBC-SD in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Avastin used in the positive controlgroup was administered once every 2 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 33 inhibition effect of polypeptide I on heterotransplanted humangallbladder cancer GBC-SD in nude mice dose (mg/kg/ initial weightinitial final weight final tumor tumor group time) (g) number (g) numberweight (g) inhibition rate control — 20.09 ± 0.34 12 23.11 ± 0.70 121.20 ± 0.30 — avastin 10 20.13 ± 0.65 8 20.89 ± 0.61 7 0.25 ± 0.06**78.85% endostar (rh- 2.5 20.11 ± 0.59 8 23.13 ± 0.38 7 0.71 ± 0.1540.83% endostatin) Polypeptide 3 20.88 ± 0.79 8 22.89 ± 0.51 8 0.50 ±0.11* 58.33% I (high) Polypeptide 1.5 20.08 ± 0.59 8 23.04 ± 0.55 8 0.42± 0.10** 65.00% I (medium) Polypeptide 0.75 19.70 ± 0.52 8 22.95 ± 0.468 0.52 ± 0.11* 56.67% I (low)

TABLE 34 inhibition effect of polypeptide II on heterotransplanted humangallbladder cancer GBC-SD in nude mice dose tumor (mg/kg/ initial weightinitial final weight final weight tumor group time) (g) number (g)number (g) inhibition rate control — 20.09 ± 0.34 12 23.11 ± 0.70 121.20 ± 0.30 — avastin 10 20.13 ± 0.65 8 20.89 ± 0.61 7 0.25 ± 0.06**78.85% endostar (rh- 2.5 20.11 ± 0.59 8 23.13 ± 0.38 7 0.71 ± 0.1540.83% endostatin) polypeptide 3 20.06 ± 0.63 8 23.10 ± 0.64 8 0.47 ±0.11* 60.48% II (high) polypeptide 1.5 19.80 ± 0.39 8 22.99 ± 0.51 80.37 ± 0.10** 69.19% II (medium) polypeptide 0.75 20.01 ± 0.51 8 22.76 ±0.51 8 0.46 ± 0.11* 62.00% II (low)

TABLE 35 inhibition effect of polypeptide III on heterotransplantedhuman gallbladder cancer GBC-SD in nude mice dose (mg/kg/ initialinitial final weight final tumor tumor group time) weight (g) number (g)number weight (g) inhibition rate control — 20.09 ± 0.34 12 23.11 ± 0.7012 1.20 ± 0.30 — avastin 10 20.13 ± 0.65 8 20.89 ± 0.61 7 0.25 ± 0.06**78.85% endostar (rh- 2.5 20.11 ± 0.59 8 23.13 ± 0.38 7 0.71 ± 0.1540.83% endostatin) polypeptide 0.75 20.22 ± 0.40 8 23.10 ± 0.56 8 0.44 ±0.11* 63.73% III (high) polypeptide 0.375 20.10 ± 0.56 8 22.85 ± 0.57 80.30 ± 0.09** 74.62% III (medium) polypeptide 0.1875 20.05 ± 0.52 822.94 ± 0.51 8 0.43 ± 0.09* 64.55% III (low)RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman gallbladder cancer GBC-SD in nude mice is shown in Table 33. Theinhibition rate of avastin on heterotransplanted human gallbladdercancer GBC-SD in nude mice was 78.85%; the body weight of mice from theavastin group presents no significant change in contrast with that fromthe negative control group. The inhibition rates of polypeptide I athigh, medium and low doses on heterotransplanted human gallbladdercancer GBC-SD in nude mice were 58.33%, 65.00% and 56.67% respectively.The tumor volume of mice from both the high-dose group and low-dosegroup presented significant difference in contrast with that from thenegative control group; the tumor volume of mice from the medium-dosegroup presented extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

The inhibition effect of polypeptide II on heterotransplanted humangallbladder cancer GBC-SD in nude mice is shown in Table 34. Theinhibition rate of avastin on heterotransplanted human gallbladdercancer GBC-SD in nude mice was 78.85%; the body weight of mice from theavastin group presents no significant change in contrast with that fromthe negative control group. The inhibition rates of polypeptide II athigh, medium and low doses on heterotransplanted human gallbladdercancer GBC-SD in nude mice were 60.48%, 69.19% and 62.00% respectively.The tumor volume of mice from both the high-dose group and low-dosegroup presented significant difference in contrast with that from thenegative control group; the tumor volume of mice from the medium-dosegroup presented extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

The inhibition effect of polypeptide III on heterotransplanted humangallbladder cancer GBC-SD in nude mice is shown in Table 35. Theinhibition rate of avastin on heterotransplanted human gallbladdercancer GBC-SD in nude mice was 78.85%; the body weight of mice from theavastin group presents no significant change in contrast with that fromthe negative control group. The inhibition rates of polypeptide III athigh, medium and low doses on heterotransplanted human gallbladdercancer GBC-SD in nude mice were 63.73%, 74.62% and 64.55% respectively.The tumor volume of mice from both the high-dose group and low-dosegroup presents significant difference in contrast with that from thenegative control group; the tumor volume of mice from the medium-dosegroup presented extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

Embodiment 15 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Bladder Cancer HT1376 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Avastin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 36 inhibition effect of polypeptide I on heterotransplanted humanbladder cancer HT1376 in nude mice dose initial weight initial finalfinal tumor tumor group (mg/kg/time) (g) number weight (g) number weight(g) inhibition rate control — 20.21 ± 0.60 12 23.03 ± 0.43 12 1.26 ±0.32 — avastin 10 19.83 ± 0.58 8 20.94 ± 0.47 7 0.24 ± 0.06** 79.60%endostar (rh- 2.5 20.15 ± 0.52 8 22.99 ± 0.62 7 0.73 ± 0.16 42.06%endostatin) polypeptide 3 19.84 ± 0.55 8 23.14 ± 0.54 8 0.64 ± 0.1349.20% I (high) polypeptide 1.5 19.76 ± 0.43 8 22.88 ± 0.66 8 0.55 ±0.09* 56.34% I (medium) polypeptide 0.75 20.19 ± 0.60 8 23.17 ± 0.58 80.59 ± 0.16 53.17% I (low)

TABLE 37 inhibition effect of polypeptide II on heterotransplanted humanbladder cancer HT1376 in nude mice tumor dose initial initial finalweight final weight tumor group (mg/kg/time) weight (g) number (g)number (g) inhibition rate control — 20.21 ± 0.60 12 23.03 ± 0.43 121.26 ± 0.32 — avastin 10 19.83 ± 0.58 8 20.94 ± 0.47 7 0.24 ± 0.06**79.60% endostar (rh- 2.5 20.15 ± 0.52 8 22.99 ± 0.62 7 0.73 ± 0.1642.06% endostatin) polypeptide 3 19.85 ± 0.55 8 23.21 ± 0.62 8 0.47 ±0.12* 60.97% II (high) polypeptide 1.5 20.01 ± 0.66 8 22.88 ± 0.63 80.35 ± 0.09** 71.10% II (medium) polypeptide 0.75 20.00 ± 0.67 8 22.86 ±0.63 8 0.39 ± 0.10** 67.62% II (low)

TABLE 38 inhibition effect of polypeptide III on heterotransplantedhuman bladder cancer HT1376 in nude mice dose (mg/kg/ initial initialfinal weight final tumor tumor group time) weight (g) number (g) numberweight (g) inhibition rate control — 20.21 ± 0.60 12 23.03 ± 0.43 121.26 ± 0.32 — avastin 10 19.83 ± 0.58 8 20.94 ± 0.47 7 0.24 ± 0.06**79.60% endostar (rh- 2.5 20.15 ± 0.52 8 22.99 ± 0.62 7 0.73 ± 0.1642.06% endostatin) polypeptide 0.75 20.12 ± 0.70 8 22.90 ± 0.69 8 0.38 ±0.10** 67.92% III (high) polypeptide 0.375 20.13 ± 0.67 8 22.85 ± 0.46 80.28 ± 0.08** 76.94% III (medium) polypeptide 0.1875 19.89 ± 0.62 823.20 ± 0.61 8 0.33 ± 0.09** 72.55% III (low)RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman bladder cancer HT1376 in nude mice is shown in Table 36. Theinhibition rate of avastin on heterotransplanted human bladder cancerHT1376 in nude mice was 79.60%; the body weight of mice from the avastingroup presented no significant change in contrast with that from thenegative control group. The inhibition rates of polypeptide I at high,medium and low doses on heterotransplanted human bladder cancer HT1376in nude mice were 49.20%, 56.34% and 53.17% respectively. The tumorvolume of mice from the medium-dose group exhibited significantdifference in contrast with that from the negative control group;meanwhile, animals from the polypeptide groups showed no significantchange in body weight, and no obvious toxic and side effects wereobserved in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanbladder cancer HT1376 in nude mice is shown in Table 37. The inhibitionrate of avastin on heterotransplanted human bladder cancer HT1376 innude mice was 79.60%; the body weight of mice from the avastin grouppresented no significant change in contrast with that from the negativecontrol group. The inhibition rates of polypeptide II at high, mediumand low doses on heterotransplanted human bladder cancer HT1376 in nudemice were 60.97%, 71.10% and 67.62% respectively. The tumor volume ofmice from the high-dose group presented significant difference incontrast with that from the negative control group; the tumor volume ofmice from both the medium-dose group and the low-dose group presentedextremely significant difference in contrast with that from the negativecontrol group; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide III on heterotransplanted humanbladder cancer HT1376 in nude mice is shown in Table 38. The inhibitionrate of avastin on heterotransplanted human bladder cancer HT1376 innude mice was 79.60%; the body weight of mice from the avastin grouppresented no significant change in contrast with that from the negativecontrol group. The inhibition rates of polypeptide III at high, mediumand low doses on heterotransplanted human bladder cancer HT1376 in nudemice were 67.92%, 76.94% and 72.55% respectively. The tumor volume ofmice from all polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

Embodiment 16 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Pancreatic Cancer SW-1990 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Avastin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 39 inhibition effect of polypeptide I on heterotransplanted humanpancreatic cancer SW-1990 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 19.87 ± 0.41 12 23.08 ± 0.59 12 1.29 ±0.32  — avastin 10 19.94 ± 0.59 8 20.99 ± 0.66 7 0.27 ± 0.07** 79.07%endostar (rh-endostatin) 2.5 19.88 ± 0.50 8 22.87 ± 0.57 7 0.65 ± 0.14 49.66% polypeptide I (high) 3 20.16 ± 0.45 8 22.86 ± 0.65 8 0.58 ±0.10*  55.04% polypeptide I (medium) 1.5 20.31 ± 0.50 8 23.03 ± 0.65 80.47 ± 0.08** 63.57% polypeptide I (low) 0.75 20.09 ± 0.56 8 23.06 ±0.64 8 0.51 ± 0.09** 60.47%

TABLE 40 inhibition effect of polypeptide II on heterotransplanted humanpancreatic cancer SW-1990 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 19.87 ± 0.41 12 23.08 ± 0.59 12 1.29 ±0.32  — avastin 10 19.94 ± 0.59 8 20.99 ± 0.66 7 0.27 ± 0.07** 79.07%endostar (rh-endostatin) 2.5 19.88 ± 0.50 8 22.87 ± 0.57 7 0.65 ± 0.14 49.66% polypeptide II (high) 3 20.21 ± 0.64 8 23.11 ± 0.61 8 0.45 ±0.10** 65.05% polypeptide II (medium) 1.5 19.76 ± 0.55 8  22.8 ± 0.57 80.35 ± 0.09** 72.97% polypeptide II (low) 0.75 19.91 ± 0.58 8 22.80 ±0.57 8 0.39 ± 0.10** 70.09%

TABLE 41 inhibition effect of polypeptide III on heterotransplantedhuman pancreatic cancer SW-1990 in nude mice dose initial weight initialfinal weight final tumor weight tumor inhi- group (mg/kg/time) (g)number (g) number (g) bition rate control — 19.87 ± 0.41 12 23.08 ± 0.5912 1.29 ± 0.32  — avastin 10 19.94 ± 0.59 8 20.99 ± 0.66 7 0.27 ± 0.07**79.07% endostar (rh-endostatin) 2.5 19.88 ± 0.50 8 22.87 ± 0.57 7 0.65 ±0.14  49.66% polypeptide III(high) 0.75 20.28 ± 0.53 8 23.00 ± 0.39 80.37 ± 0.08** 71.01% polypeptide III(medium) 0.375 20.05 ± 0.60 8 22.93± 0.56 8 0.28 ± 0.06** 78.64% polypeptide III(low) 0.1875 20.27 ± 0.67 823.21 ± 0.61 8 0.33 ± 0.08** 74.68%RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman pancreatic cancer SW-1990 in nude mice is shown in Table 39. Theinhibition rate of avastin on heterotransplanted human pancreatic cancerSW-1990 in nude mice was 79.07%; the body weight of mice from theavastin group presented no significant change in contrast with that fromthe negative control group. The inhibition rates of polypeptide I athigh, medium and low doses on heterotransplanted human pancreatic cancerSW-1990 in nude mice were 55.04%, 63.57% and 60.47% respectively. Thetumor volume of mice from all polypeptide groups, including thehigh-dose group, the medium-dose group and the low-dose group, exhibitedextremely significant difference in contrast with that from the negativecontrol group; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanpancreatic cancer SW-1990 in nude mice is shown in Table 40. Theinhibition rate of avastin on heterotransplanted human pancreatic cancerSW-1990 in nude mice was 79.07%; the body weight of mice from theavastin group presented no significant change in contrast with that fromthe negative control group. The inhibition rates of polypeptide II athigh, medium and low doses on heterotransplanted human pancreatic cancerSW-1990 in nude mice were 65.05%, 72.97% and 70.09% respectively. Thetumor volume of mice from all polypeptide groups, including thehigh-dose group, the medium-dose group and the low-dose group, exhibitedextremely significant difference in contrast with that from the negativecontrol group; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide III on heterotransplanted humanpancreatic cancer SW-1990 in nude mice is shown in Table 41. Theinhibition rate of avastin on heterotransplanted human pancreatic cancerSW-1990 in nude mice was 79.07%; the body weight of mice from theavastin group presented no significant change in contrast with that fromthe negative control group. The inhibition rates of polypeptide III athigh, medium and low doses on heterotransplanted human pancreatic cancerSW-1990 in nude mice were 71.01%, 78.64% and 74.68% respectively. Thetumor volume of mice from all polypeptide groups, including thehigh-dose group, the medium-dose group and the low-dose group, exhibitedextremely significant difference in contrast with that from the negativecontrol group; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

Embodiment 17 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Esophageal Cancer Ec109 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Avastin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 42 inhibition effect of polypeptide I on heterotransplanted humanesophageal cancer Ec109 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 20.19 ± 0.57 12 22.82 ± 0.63 12 1.53 ±0.38  — avastin 10 20.04 ± 0.55 8 20.93 ± 0.51 7 0.47 ± 0.10** 69.00%endostar (rh-endostatin) 2.5 19.86 ± 0.49 8 22.92 ± 0.45 7 0.89 ± 0.24 41.57% polypeptide I (high) 3 20.00 ± 0.67 8 22.94 ± 0.64 7 0.54 ±0.08** 64.71% polypeptide I (medium) 1.5 20.09 ± 0.56 8 23.06 ± 0.64 80.47 ± 0.06** 69.00% polypeptide I (low) 0.75 20.00 ± 0.58 8 22.63 ±0.57 8 0.53 ± 0.08** 65.36%

TABLE 43 inhibition effect of polypeptide II on heterotransplanted humanesophageal cancer Ec109 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 20.19 ± 0.57 12 22.82 ± 0.63 12 1.53 ±0.38  — avastin 10 20.04 ± 0.55 8 20.93 ± 0.51 7 0.47 ± 0.10** 69.00%endostar (rh-endostatin) 2.5 19.86 ± 0.49 8 22.92 ± 0.45 7 0.89 ± 0.24 41.57% polypeptide II (high) 3 19.93 ± 0.64 8 22.90 ± 0.59 8 0.71 ±0.15*  53.34% polypeptide II (medium) 1.5 20.06 ± 0.56 8 23.08 ± 0.58 80.55 ± 0.12** 63.88% polypeptide II (low) 0.75 20.05 ± 0.66 8 22.97 ±0.58 8 0.62 ± 0.13*  59.65%

TABLE 44 inhibition effect of polypeptide III on heterotransplantedhuman esophageal cancer Ec109 in nude mice dose initial weight initialfinal weight final tumor weight tumor inhi- group (mg/kg/time) (g)number (g) number (g) bition rate control — 20.19 ± 0.57 12 22.82 ± 0.6312 1.53 ± 0.38  — avastin 10 20.04 ± 0.55 8 20.93 ± 0.51 7 0.47 ± 0.10**69.00% endostar (rh-endostatin) 2.5 19.86 ± 0.49 8 22.92 ± 0.45 7 0.89 ±0.24  41.57% polypeptide III(high) 0.75 19.98 ± 0.57 8 23.17 ± 0.67 80.62 ± 0.18*  59.75% polypeptide III(medium) 0.375 20.18 ± 0.53 8 23.31± 0.73 8 0.50 ± 0.12** 67.13% polypeptide III(low) 0.1875 20.06 ± 0.44 823.14 ± 0.52 8 0.53 ± 0.14** 65.63%RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman esophageal cancer Ec109 in nude mice is shown in Table 42. Theinhibition rate of avastin on heterotransplanted human esophageal cancerEc109 in nude mice was 69.00%; the body weight of mice from the avastingroup presented no significant change in contrast with that from thenegative control group. The inhibition rates of polypeptide I at high,medium and low doses on heterotransplanted human esophageal cancer Ec109in nude mice were 64.71%, 69.00% and 65.36% respectively. The tumorvolume of mice from all polypeptide groups, including the high-dosegroup, the medium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanesophageal cancer Ec109 in nude mice is shown in Table 43. Theinhibition rate of avastin on heterotransplanted human esophageal cancerEc109 in nude mice was 69.00%; the body weight of mice from the avastingroup presented no significant change in contrast with that from thenegative control group. The inhibition rates of polypeptide II at high,medium and low doses on heterotransplanted human esophageal cancer Ec109in nude mice were 53.34%, 63.88% and 59.65% respectively. The tumorvolume of mice from both the high-dose group and the low-dose grouppresented significant difference in contrast with that from the negativecontrol group; the tumor volume of mice from the medium-dose grouppresented extremely significant difference in contrast with that fromthe negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

The inhibition effect of polypeptide III on heterotransplanted humanesophageal cancer Ec109 in nude mice is shown in Table 44. Theinhibition rate of avastin on heterotransplanted human esophageal cancerEc109 in nude mice was 69.00%; the body weight of mice from the avastingroup presented no significant change in contrast with that from thenegative control group. The inhibition rates of polypeptide III at high,medium and low doses on heterotransplanted human esophageal cancer Ec109in nude mice were 59.75%, 67.13% and 65.63% respectively. The tumorvolume of mice from the high-dose group presented significant differencein contrast with that from the negative control group; the tumor volumeof mice from both the medium-dose group and the low-dose group presentedextremely significant difference in contrast with that from the negativecontrol group; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

Embodiment 18 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Colon Cancer HT-29 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Cisplatin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 45 inhibition effect of polypeptide I on heterotransplanted humancolon cancer HT-29 in nude mice dose initial weight initial final weightfinal tumor weight tumor inhi- group (mg/kg/time) (g) number (g) number(g) bition rate control — 20.09 ± 0.64 12 22.78 ± 0.62 12 1.44 ± 0.36  —cisplatin 10 20.17 ± 0.56 8 17.75 ± 0.53 7 0.30 ± 0.05** 79.17% endostar(rh-endostatin) 2.5 19.96 ± 0.60 8 22.91 ± 0.61 8 0.58 ± 0.14  59.50%polypeptide I (high) 3 19.95 ± 1.21 10 19.60 ± 1.26 10 0.56 ± 0.15**61.11% polypeptide I (medium) 1.5 20.15 ± 0.97 10 19.67 ± 1.41 10 0.49 ±0.12** 65.97% polypeptide I (low) 0.75 20.00 ± 1.22 10 20.40 ± 1.26 100.46 ± 0.13** 68.05%

TABLE 46 inhibition effect of polypeptide II on heterotransplanted humancolon cancer HT-29 in nude mice dose initial weight initial final weightfinal tumor weight tumor inhi- group (mg/kg/time) (g) number (g) number(g) bition rate control — 20.09 ± 0.64 12 22.78 ± 0.62 12 1.44 ± 0.36  —cisplatin 10 20.17 ± 0.56 8 17.75 ± 0.53 7 0.30 ± 0.05** 79.17% endostar(rh-endostatin) 2.5 19.96 ± 0.60 8 22.91 ± 0.61 8 0.58 ± 0.14  59.50%polypeptide II (high) 3 19.90 ± 0.65 8 22.77 ± 0.60 8 0.39 ± 0.09**72.93% polypeptide II (medium) 1.5 19.80 ± 0.54 8 23.13 ± 0.71 8 0.26 ±0.07** 81.96% polypeptide II (low) 0.75 19.89 ± 0.61 8 22.81 ± 0.71 80.31 ± 0.07** 78.32%

TABLE 47 inhibition effect of polypeptide III on heterotransplantedhuman colon cancer HT-29 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 20.09 ± 0.64 12 22.78 ± 0.62 12 1.44 ±0.36  — cisplatin 10 20.17 ± 0.56 8 17.75 ± 0.53 7 0.30 ± 0.05** 79.17%endostar (rh-endostatin) 2.5 19.96 ± 0.60 8 22.91 ± 0.61 8 0.58 ± 0.14 59.50% polypeptide III(high) 0.75 20.12 ± 0.67 8 22.90 ± 0.52 8 0.30 ±0.09** 79.11% polypeptide III(medium) 0.375 20.12 ± 0.58 8 23.04 ± 0.638 0.21 ± 0.06** 85.62% polypeptide III(low) 0.1875 20.28 ± 0.70 8 22.84± 0.52 8 0.23 ± 0.07** 83.70%RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman colon cancer HT-29 in nude mice is shown in Table 45. Theinhibition rate of the cisplatin group on heterotransplanted human coloncancer HT-29 in nude mice was 79.17%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide I at high, medium and low doses onheterotransplanted human colon cancer HT-29 in nude mice were 61.11%,65.97% and 68.05% respectively. The tumor volume of mice from allpolypeptide groups, including the high-dose group, the medium-dose groupand the low-dose group, exhibited extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide II on heterotransplanted humancolon cancer HT-29 in nude mice is shown in Table 46. The inhibitionrate of the cisplatin group on heterotransplanted human colon cancerHT-29 in nude mice was 79.17%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide II at high, medium and low doses onheterotransplanted human colon cancer HT-29 in nude mice were 72.93%,81.96% and 78.32% respectively. The tumor volume of mice from allpolypeptide groups, including the high-dose group, the medium-dose groupand the low-dose group, exhibited extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide III on heterotransplanted humancolon cancer HT-29 in nude mice is shown in Table 47. The inhibitionrate of the cisplatin group on heterotransplanted human colon cancerHT-29 in nude mice was 79.17%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide III at high, medium and low doses onheterotransplanted human colon cancer HT-29 in nude mice were 79.11%,85.62% and 83.70% respectively. The tumor volume of mice from allpolypeptide groups, including the high-dose group, the medium-dose groupand the low-dose group, exhibited extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

Embodiment 19 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Thyroid Cancer SW-579 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Cisplatin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 48 inhibition effect of polypeptide I on heterotransplanted humanthyroid cancer SW-579 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 19.95 ± 0.54 12 22.83 ± 0.56 12 1.31 ±0.30  — cisplatin 10 20.15 ± 0.66 8 18.25 ± 0.65 7 0.34 ± 0.07** 74.09%endostar (rh-endostatin) 2.5 20.07 ± 0.61 8 22.70 ± 0.54 8 0.88 ± 0.19 32.82% polypeptide I (high) 3 19.75 ± 0.65 10 20.88 ± 0.85 10 0.55 ±0.12*  58.01% polypeptide I (medium) 1.5 19.63 ± 0.75 10 20.13 ± 1.03 100.46 ± 0.16** 64.89% polypeptide I (low) 0.75 20.25 ± 0.65 10 22.25 ±1.71 10 0.47 ± 0.14** 64.12%

TABLE 49 inhibition effect of polypeptide II on heterotransplanted humanthyroid cancer SW-579 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 19.95 ± 0.54 12 22.83 ± 0.56 12 1.31 ±0.30  — cisplatin 10 20.15 ± 0.66 8 18.25 ± 0.65 7 0.34 ± 0.07** 74.09%endostar (rh-endostatin) 2.5 20.07 ± 0.61 8 22.70 ± 0.54 8 0.88 ± 0.19 32.82% polypeptide II (high) 3 19.82 ± 0.39 8 23.15 ± 0.67 8 0.57 ±0.15*  56.59% polypeptide II (medium) 1.5 19.88 ± 0.50 8 23.23 ± 0.67 80.43 ± 0.10** 66.94% polypeptide II (low) 0.75 19.64 ± 0.44 8 22.92 ±0.67 8 0.51 ± 0.13** 60.97%

TABLE 50 inhibition effect of polypeptide III on heterotransplantedhuman thyroid cancer SW-579 in nude mice dose initial weight initialfinal weight final tumor weight tumor inhi- group (mg/kg/time) (g)number (g) number (g) bition rate control — 19.95 ± 0.54 12 22.83 ± 0.5612 1.31 ± 0.30  — cisplatin 10 20.15 ± 0.66 8 18.25 ± 0.65 7 0.34 ±0.07** 74.09% endostar (rh-endostatin) 2.5 20.07 ± 0.61 8 22.70 ± 0.54 80.88 ± 0.19  32.82% polypeptide III(high) 0.75 19.76 ± 0.53 8 22.56 ±0.55 8 0.48 ± 0.14** 63.38% polypeptide III(medium) 0.375 19.96 ± 0.54 823.09 ± 0.54 8 0.39 ± 0.08** 70.58% polypeptide III(low) 0.1875 19.98 ±0.55 8 23.18 ± 0.66 8 0.44 ± 0.09** 66.40%RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman thyroid cancer SW-579 in nude mice is shown in Table 48. Theinhibition rate of the cisplatin group on heterotransplanted humanthyroid cancer SW-579 in nude mice was 74.09%, however, thischemotherapy greatly reduced the body weight of animals; mice treated inthis way showed lighter body weight and more apparent toxic and sideeffects than those from the negative control group and the polypeptidegroups. The inhibition rates of polypeptide I at high, medium and lowdoses on heterotransplanted human thyroid cancer SW-579 in nude micewere 58.01%, 64.89% and 64.12% respectively. The tumor volume of micefrom the high-dose group presented significant difference in contrastwith that from the negative control group; the tumor volume of mice fromboth the medium-dose group and the low-dose group presented extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanthyroid cancer SW-579 in nude mice is shown in Table 49. The inhibitionrate of the cisplatin group on heterotransplanted human thyroid cancerSW-579 in nude mice was 74.09%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide II at high, medium and low doses onheterotransplanted human thyroid cancer SW-579 in nude mice were 56.59%,66.94% and 60.97% respectively. The tumor volume of mice from thehigh-dose group presented significant difference in contrast with thatfrom the negative control group; the tumor volume of mice from both themedium-dose group and the low-dose group presented extremely significantdifference in contrast with that from the negative control group;meanwhile, animals from the polypeptide groups showed no significantchange in body weight, and no obvious toxic and side effects wereobserved in contrast with the negative control group.

The inhibition effect of polypeptide III on heterotransplanted humanthyroid cancer SW-579 in nude mice is shown in Table 50. The inhibitionrate of the cisplatin group on heterotransplanted human thyroid cancerSW-579 in nude mice was 74.09%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide III at high, medium and low doses onheterotransplanted human thyroid cancer SW-579 in nude mice were 63.38%,70.58% and 66.40% respectively. The tumor volume of mice from allpolypeptide groups, including the high-dose group, the medium-dose groupand the low-dose group, exhibited extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

Embodiment 20 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Renal Cancer A498 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Cisplatin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 51 inhibition effect of polypeptide I on heterotransplanted humanrenal cancer A498 in nude mice dose initial weight initial final weightfinal tumor weight tumor inhi- group (mg/kg/time) (g) number (g) number(g) bition rate control — 19.99 ± 0.72 12 23.13 ± 0.51 12 1.23 ± 0.26  —cisplatin 10 20.13 ± 0.57 8 17.80 ± 0.63 7 0.25 ± 0.06** 79.83% endostar(rh-endostatin) 2.5 19.94 ± 0.65 8 22.96 ± 0.69 8 0.70 ± 0.14  43.20%polypeptide I (high) 3 20.21 ± 0.57 8 22.59 ± 0.53 8 0.57 ± 0.15* 53.65% polypeptide I (medium) 1.5 20.06 ± 0.47 8 23.26 ± 0.40 8 0.49 ±0.10** 60.16% polypeptide I (low) 0.75 20.02 ± 0.51 8 22.87 ± 0.40 80.51 ± 0.13*  58.53%

TABLE 52 inhibition effect of polypeptide II on heterotransplanted humanrenal cancer A498 in nude mice dose initial weight initial final weightfinal tumor weight tumor inhi- group (mg/kg/time) (g) number (g) number(g) bition rate control — 19.99 ± 0.72 12 23.13 ± 0.51 12 1.23 ± 0.26  —cisplatin 10 20.13 ± 0.57 8 17.80 ± 0.63 7 0.25 ± 0.06** 79.83% endostar(rh-endostatin) 2.5 19.94 ± 0.65 8 22.96 ± 0.69 8 0.70 ± 0.14  43.20%polypeptide II (high) 3 20.05 ± 0.52 8 22.93 ± 0.51 8 0.43 ± 0.11**64.90% polypeptide II (medium) 1.5 19.91 ± 0.57 8 23.13 ± 0.58 8 0.35 ±0.09** 71.41% polypeptide II (low) 0.75 19.94 ± 0.56 8 23.14 ± 0.58 80.41 ± 0.11** 67.03%

TABLE 53 inhibition effect of polypeptide III on heterotransplantedhuman renal cancer A498 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 19.99 ± 0.72 12 23.13 ± 0.51 12 1.23 ±0.26  — cisplatin 10 20.13 ± 0.57 8 17.80 ± 0.63 7 0.25 ± 0.06** 79.83%endostar (rh-endostatin) 2.5 19.94 ± 0.65 8 22.96 ± 0.69 8 0.70 ± 0.14 43.20% polypeptide III(high) 0.75 19.68 ± 0.59 8 23.18 ± 0.50 8 0.41 ±0.12** 66.36% polypeptide III(medium) 0.375 19.83 ± 0.65 8 22.92 ± 0.598 0.30 ± 0.07** 75.36% polypeptide III(low) 0.1875 19.97 ± 0.66 8 22.82± 0.69 8 0.36 ± 0.10** 70.74%RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman renal cancer A498 in nude mice is shown in Table 51. Theinhibition rate of the cisplatin group on heterotransplanted human renalcancer A498 in nude mice was 79.83%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide I at high, medium and low doses onheterotransplanted human renal cancer A498 in nude mice were 53.65%,60.16% and 58.53% respectively. The tumor volume of mice from both thehigh-dose group and low-dose group presented significant difference incontrast with that from the negative control group; the tumor volume ofmice from the medium-dose group presented extremely significantdifference in contrast with that from the negative control group;meanwhile, animals from the polypeptide groups showed no significantchange in body weight, and no obvious toxic and side effects wereobserved in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanrenal cancer A498 in nude mice is shown in Table 52. The inhibition rateof the cisplatin group on heterotransplanted human renal cancer A498 innude mice was 79.83%, however, this chemotherapy greatly reduced thebody weight of animals; mice treated in this way showed lighter bodyweight and more apparent toxic and side effects than those from thenegative control group and the polypeptide groups. The inhibition ratesof polypeptide II at high, medium and low doses on heterotransplantedhuman renal cancer A498 in nude mice were 64.90%, 71.41% and 67.03%respectively. The tumor volume of mice from all polypeptide groups,including the high-dose group, the medium-dose group and the low-dosegroup, exhibited extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

The inhibition effect of polypeptide III on heterotransplanted humanrenal cancer A498 in nude mice is shown in Table 53. The inhibition rateof the cisplatin group on heterotransplanted human renal cancer A498 innude mice was 79.83%, however, this chemotherapy greatly reduced thebody weight of animals; mice treated in this way showed lighter bodyweight and more apparent toxic and side effects than those from thenegative control group and the polypeptide groups. The inhibition ratesof polypeptide III at high, medium and low doses on heterotransplantedhuman renal cancer A498 in nude mice were 66.36%, 75.36% and 70.74%respectively. The tumor volume of mice from all polypeptide groups,including the high-dose group, the medium-dose group and the low-dosegroup, exhibited extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

Embodiment 21 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Ovarian Cancer SK-OV-3 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Cisplatin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 54 inhibition effect of polypeptide I on heterotransplanted humanovarian cancer SK-OV-3 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 19.87 ± 0.43 12 23.03 ± 0.59 12 1.34 ±0.27  — cisplatin 10 20.04 ± 0.58 8 18.15 ± 0.57 7 0.29 ± 0.06** 78.36%endostar (rh-endostatin) 2.5 19.99 ± 0.71 8 23.19 ± 0.72 8 0.88 ± 0.17 34.32% polypeptide I (high) 3 20.03 ± 0.61 8 23.16 ± 0.51 8 0.47 ±0.12** 67.13% polypeptide I (medium) 1.5 20.05 ± 0.58 8 22.96 ± 0.59 80.39 ± 0.07** 70.89% polypeptide I (low) 0.75 19.97 ± 0.62 8 23.09 ±0.59 8 0.41 ± 0.10** 69.40%

TABLE 55 inhibition effect of polypeptide II on heterotransplanted humanovarian cancer SK-OV-3 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 19.87 ± 0.43 12 23.03 ± 0.59 12 1.34 ±0.27  — cisplatin 10 20.04 ± 0.58 8 18.15 ± 0.57 7 0.29 ± 0.06** 78.36%endostar (rh-endostatin) 2.5 19.99 ± 0.71 8 23.19 ± 0.72 8 0.88 ± 0.17 34.32% polypeptide II (high) 3 20.22 ± 0.52 8 22.97 ± 0.65 8 0.49 ±0.14** 63.25% polypeptide II (medium) 1.5 19.83 ± 0.58 8 23.32 ± 0.50 80.36 ± 0.08** 72.76% polypeptide II (low) 0.75 19.91 ± 0.61 8 23.07 ±0.50 8 0.42 ± 0.10** 68.36%

TABLE 56 inhibition effect of polypeptide III on heterotransplantedhuman ovarian cancer SK-OV-3 in nude mice dose initial weight initialfinal weight final tumor weight tumor inhi- group (mg/kg/time) (g)number (g) number (g) bition rate control — 19.87 ± 0.43 12 23.03 ± 0.5912 1.34 ± 0.27  — cisplatin 10 20.04 ± 0.58 8 18.15 ± 0.57 7 0.29 ±0.06** 78.36% endostar (rh-endostatin) 2.5 19.99 ± 0.71 8 23.19 ± 0.72 80.88 ± 0.17  34.32% polypeptide 0.75 20.18 ± 0.58 8 22.95 ± 0.64 8 0.40± 0.11** 69.98% III(high) polypeptide III(medium) 0.375 19.91 ± 0.55 822.92 ± 0.70 8 0.31 ± 0.07** 76.63% polypeptide III(low) 0.1875 19.55 ±0.57 8 22.83 ± 0.50 8 0.35 ± 0.09** 73.87%RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman ovarian cancer SK-OV-3 in nude mice is shown in Table 54. Theinhibition rate of the cisplatin group on heterotransplanted humanovarian cancer SK-OV-3 in nude mice was 78.36%, however, thischemotherapy greatly reduced the body weight of animals; mice treated inthis way showed lighter body weight and more apparent toxic and sideeffects than those from the negative control group and the polypeptidegroups. The inhibition rates of polypeptide I at high, medium and lowdoses on heterotransplanted human ovarian cancer SK-OV-3 in nude micewere 67.13%, 70.89% and 69.40% respectively. The tumor volume of micefrom all polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanovarian cancer SK-OV-3 in nude mice is shown in Table 55. The inhibitionrate of the cisplatin group on heterotransplanted human ovarian cancerSK-OV-3 in nude mice was 78.36%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide II at high, medium and low doses onheterotransplanted human ovarian cancer SK-OV-3 in nude mice were63.25%, 72.76% and 68.36% respectively. The tumor volume of mice fromall polypeptide groups, including the high-dose group, the medium-dosegroup and the low-dose group, exhibited extremely significant differencein contrast with that from the negative control group; meanwhile,animals from the polypeptide groups showed no significant change in bodyweight, and no obvious toxic and side effects were observed in contrastwith the negative control group.

The inhibition effect of polypeptide III on heterotransplanted humanovarian cancer SK-OV-3 in nude mice is shown in Table 56. The inhibitionrate of the cisplatin group on heterotransplanted human ovarian cancerSK-OV-3 in nude mice was 78.36%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide III at high, medium and low doses onheterotransplanted human ovarian cancer SK-OV-3 in nude mice were69.98%, 76.63% and 73.87% respectively. The tumor volume of mice fromall polypeptide groups, including the high-dose group, the medium-dosegroup and the low-dose group, exhibited extremely significant differencein contrast with that from the negative control group; meanwhile,animals from the polypeptide groups showed no significant change in bodyweight, and no obvious toxic and side effects were observed in contrastwith the negative control group.

Embodiment 22 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedSarcoma HT-1080 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. 5-fluorouracil (5-FU) used in thepositive control group was administered once every 3 days through tailvein injection, while drugs of all other groups were administered ondaily basis through tail vein injection.

TABLE 57 inhibition effect of polypeptide I on heterotransplantedsarcoma HT-1080 in nude mice dose initial weight initial final weightfinal tumor weight tumor inhi- group (mg/kg/time) (g) number (g) number(g) bition rate control — 20.09 ± 0.66 12 23.01 ± 0.48 12 1.37 ± 0.35  —5-Fu 10 19.94 ± 0.58 8 17.88 ± 0.68 7 0.30 ± 0.07** 78.10% endostar(rh-endostatin) 2.5 19.88 ± 0.79 8 22.89 ± 0.51 8 0.69 ± 0.15  49.72%polypeptide I (high) 3 20.11 ± 0.59 8 23.13 ± 0.38 7 0.49 ± 0.14**64.23% polypeptide I (medium) 1.5 20.06 ± 0.63 8 23.10 ± 0.64 8 0.36 ±0.08** 73.72% polypeptide I (low) 0.75 19.80 ± 0.39 8 22.99 ± 0.51 80.42 ± 0.10** 69.34%

TABLE 58 inhibition effect of polypeptideIIon heterotransplanted sarcomaHT-1080 in nude mice dose initial weight initial final weight finaltumor weight tumor inhi- group (mg/kg/time) (g) number (g) number (g)bition rate control — 20.09 ± 0.66 12 23.01 ± 0.48 12 1.37 ± 0.35  —5-Fu 10 19.94 ± 0.58 8 17.88 ± 0.68 7 0.30 ± 0.07** 78.10% endostar(rh-endostatin) 2.5 19.88 ± 0.79 8 22.89 ± 0.51 8 0.69 ± 0.15  49.72%polypeptide II (high) 3 20.08 ± 0.59 8 23.04 ± 0.55 8 0.45 ± 0.11**67.06% polypeptide II (medium) 1.5 19.70 ± 0.52 8 22.95 ± 0.46 8 0.35 ±0.07** 74.43% polypeptide II (low) 0.75 20.28 ± 0.61 8 22.93 ± 0.46 80.40 ± 0.11** 70.60%

TABLE 59 inhibition effect of polypeptideIIIon heterotransplantedsarcoma HT-1080 in nude mice dose initial weight initial final weightfinal tumor weight tumor inhi- group (mg/kg/time) (g) number (g) number(g) bition rate control — 20.09 ± 0.66 12 23.01 ± 0.48 12 1.37 ± 0.35  —5-Fu 10 19.94 ± 0.58 8 17.88 ± 0.68 7 0.30 ± 0.07** 78.10% endostar(rh-endostatin) 2.5 19.88 ± 0.79 8 22.89 ± 0.51 8 0.69 ± 0.15  49.72%polypeptide III(high) 0.75 19.89 ± 0.53 8 23.07 ± 0.56 8 0.37 ± 0.10**73.29% polypeptide III(medium) 0.375 20.31 ± 0.51 8 23.18 ± 0.57 8 0.28± 0.06** 79.90% polypeptide III(low) 0.1875 19.74 ± 0.55 8 22.92 ± 0.578 0.33 ± 0.07** 75.87%RESULTS: the inhibition effect of polypeptide I on heterotransplantedsarcoma HT-1080 in nude mice is shown in Table 57. The inhibition rateof the 5-FU group on heterotransplanted sarcoma HT-1080 in nude mice was78.10%, however, this chemotherapy greatly reduced the body weight ofanimals; mice treated in this way showed lighter body weight and moreapparent toxic and side effects than those from the negative controlgroup and the polypeptide groups. The inhibition rates of polypeptide Iat high, medium and low doses on heterotransplanted sarcoma HT-1080 innude mice were 64.23%, 73.72% and 69.34% respectively. The tumor volumeof mice from all polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted sarcomaHT-1080 in nude mice is shown in Table 58. The inhibition rate of the5-FU group on heterotransplanted sarcoma HT-1080 in nude mice was78.10%, however, this chemotherapy greatly reduced the body weight ofanimals; mice treated in this way showed lighter body weight and moreapparent toxic and side effects than those from the negative controlgroup and the polypeptide groups. The inhibition rates of polypeptide IIat high, medium and low doses on heterotransplanted sarcoma HT-1080 innude mice were 67.06%, 74.43% and 70.60% respectively. The tumor volumeof mice from the high-dose group presented significant difference incontrast with that from the negative control group; the tumor volume ofmice from both the medium-dose group and the low-dose group presentedextremely significant difference in contrast with that from the negativecontrol group; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

The inhibition effect of polypeptide III on heterotransplanted sarcomaHT-1080 in nude mice is shown in Table 59. The inhibition rate of the5-FU group on heterotransplanted sarcoma HT-1080 in nude mice was78.10%, however, this chemotherapy greatly reduced the body weight ofanimals; mice treated in this way showed lighter body weight and moreapparent toxic and side effects than those from the negative controlgroup and the polypeptide groups. The inhibition rates of polypeptideIII at high, medium and low doses on heterotransplanted sarcoma HT-1080in nude mice were 73.29%, 79.90% and 75.87% respectively. The tumorvolume of mice from all polypeptide groups, including the high-dosegroup, the medium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with that from the negative controlgroup; meanwhile, animals from the polypeptide groups showed nosignificant change in body weight, and no obvious toxic and side effectswere observed in contrast with the negative control group.

Embodiment 23 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Laryngeal Cancer Hep-2 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Avastin used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 60 inhibition effect of polypeptide I on heterotransplanted humanlaryngeal cancer Hep-2 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 20.00 ± 0.52 12 23.33 ± 0.44 12 1.12 ±0.20  — avastin 10 20.09 ± 0.70 8 20.47 ± 0.70 6 0.26 ± 0.06** 76.79%endostar (rh-endostatin) 2.5 20.18 ± 0.61 8 23.23 ± 0.67 7 0.59 ± 0.10 46.96% polypeptide I (high) 3 20.15 ± 0.52 8 22.99 ± 0.62 8 0.50 ±0.10*  55.35% polypeptide I (medium) 1.5 19.85 ± 0.55 8 23.21 ± 0.62 80.41 ± 0.16** 63.39% polypeptide I (low) 0.75 20.01 ± 0.66 8 22.88 ±0.63 8 0.43 ± 0.07** 60.90%

TABLE 61 inhibition effect of polypeptide II on heterotransplanted humanlaryngeal cancer Hep-2 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 20.00 ± 0.52 12 23.33 ± 0.44 12 1.12 ±0.20  — avastin 10 20.09 ± 0.70 8 20.47 ± 0.70 6 0.26 ± 0.06** 76.79%endostar (rh-endostatin) 2.5 20.18 ± 0.61 8 23.23 ± 0.67 7 0.59 ± 0.10 46.96% polypeptide II (high) 3 20.02 ± 0.52 8 22.66 ± 0.61 8 0.44 ±0.08*  60.76% polypeptide II (medium) 1.5 20.14 ± 0.52 8 22.98 ± 0.60 80.33 ± 0.07** 70.41% polypeptide II (low) 0.75 19.96 ± 0.52 8 22.88 ±0.70 8 0.39 ± 0.06** 64.98%

TABLE 62 inhibition effect of polypeptide III on heterotransplantedhuman laryngeal cancer Hep-2 in nude mice dose initial weight initialfinal weight final tumor weight tumor inhi- group (mg/kg/time) (g)number (g) number (g) bition rate control — 20.00 ± 0.52 12 23.33 ± 0.4412 1.12 ± 0.20 — avastin 10 20.09 ± 0.70 8 20.47 ± 0.70 6 0.26 ± 0.0676.79% endostar (rh-endostatin) 2.5 20.18 ± 0.61 8 23.23 ± 0.67 7 0.59 ±0.10 46.96% polypeptide III(high) 0.75 20.07 ± 0.53 8 23.18 ± 0.51 8 0.42 ± 0.10* 62.81% polypeptide III(medium) 0.375 20.17 ± 0.48 8 22.96± 0.57 8  0.28 ± 0.05** 75.13% polypeptide III(low) 0.1875 19.62 ± 0.528 22.94 ± 0.46 8  0.37 ± 0.08** 67.29%RESULTS: the inhibition effect of polypeptideIon heterotransplantedhuman laryngeal cancer Hep-2 in nude mice is shown in Table 60. Theinhibition rate of avastin on heterotransplanted human laryngeal cancerHep-2 in nude mice was 76.79%, and the body weight of mice from theavastin group showed no significant change. The inhibition rates ofpolypeptide I at high, medium and low doses on heterotransplanted humanlaryngeal cancer Hep-2 in nude mice were 55.35%, 63.39% and 60.90%respectively. The tumor volume of mice from the high-dose grouppresented significant difference in contrast with that from the negativecontrol group; the tumor volume of mice from both the medium-dose groupand the low-dose group presented extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide II on heterotransplanted humanlaryngeal cancer Hep-2 in nude mice is shown in Table 61. The inhibitionrate of avastin on heterotransplanted human laryngeal cancer Hep-2 innude mice was 76.79%, and the body weight of mice from the avastin groupshowed no significant change. The inhibition rates of polypeptide II athigh, medium and low doses on heterotransplanted human laryngeal cancerHep-2 in nude mice were 60.76%, 70.41% and 64.98% respectively. Thetumor volume of mice from the high-dose group presented significantdifference in contrast with that from the negative control group; thetumor volume of mice from both the medium-dose group and the low-dosegroup presented extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

The inhibition effect of polypeptide III on heterotransplanted humanlaryngeal cancer Hep-2 in nude mice is shown in Table 62. The inhibitionrate of avastin on heterotransplanted human laryngeal cancer Hep-2 innude mice was 76.79%, and the body weight of mice from the avastin groupshowed no significant change. The inhibition rates of polypeptide III athigh, medium and low doses on heterotransplanted human laryngeal cancerHep-2 in nude mice were 62.81%, 75.13% and 67.29% respectively. Thetumor volume of mice from the high-dose group presented significantdifference in contrast with that from the negative control group; thetumor volume of mice from both the medium-dose group and the low-dosegroup presented extremely significant difference in contrast with thatfrom the negative control group; meanwhile, animals from the polypeptidegroups showed no significant change in body weight, and no obvious toxicand side effects were observed in contrast with the negative controlgroup.

Embodiment 24 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Brain Tumor SF763 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Taxol used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 63 inhibition effect of polypeptideIon heterotransplanted humanbrain tumor SF763 in nude mice dose initial weight initial final weightfinal tumor weight tumor inhi- group (mg/kg/time) (g) number (g) number(g) bition rate control — 19.89 ± 0.64 12 23.03 ± 0.81 12 1.18 ± 0.33  —taxol 10 20.14 ± 0.43 8 17.97 ± 0.63 6 0.28 ± 0.07** 76.29% polypeptideI(high) 3 19.83 ± 0.58 8 20.94 ± 0.47 8 0.47 ± 0.08** 60.16% polypeptideI(medium) 1.5 20.15 ± 0.52 8 22.99 ± 0.62 8 0.34 ± 0.07** 71.19%polypeptide I(low) 0.75 20.12 ± 0.70 8 22.90 ± 0.69 8 0.38 ± 0.06**67.80%

TABLE 64 inhibition effect of polypeptide II on heterotransplanted humanbrain tumor SF763 in nude mice dose initial weight initial final weightfinal tumor weight tumor inhi- group (mg/kg/time) (g) number (g) number(g) bition rate control — 19.89 ± 0.64 12 23.03 ± 0.81 12 1.18 ± 0.33  —taxol 10 20.14 ± 0.43 8 17.97 ± 0.63 7 0.288 ± 0.07** 76.29% polypeptideII (high) 3 19.94 ± 0.48 8 23.24 ± 0.66 8 0.41 ± 0.14* 65.48%polypeptide II (medium) 1.5 20.21 ± 0.58 8 22.88 ± 0.52 8  0.29 ± 0.07**75.02% polypeptide II (low) 0.75 20.01 ± 0.78 8 22.95 ± 0.52 8  0.35 ±0.13** 70.61%

TABLE 65 inhibition effect of polypeptide III on heterotransplantedhuman brain tumor SF763 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 19.89 ± 0.64 12 23.03 ± 0.81 12 1.18 ±0.33  — taxol 10 20.14 ± 0.43 8 17.97 ± 0.63 7 0.28 ± 0.07** 76.29%polypeptide III(high) 0.75 19.86 ± 0.48 8 23.09 ± 0.53 8 0.31 ± 0.09**74.06% polypeptide III(medium) 0.375 20.18 ± 0.64 8 23.37 ± 0.56 8 0.24± 0.05** 79.76% polypeptide III(low) 0.1875 19.99 ± 0.62 8 23.31 ± 0.578 0.32 ± 0.08** 72.82%RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman brain tumor SF763 in nude mice is shown in Table 63. Theinhibition rate of the taxol group on heterotransplanted human braintumor SF763 in nude mice was 76.29%, however, this chemotherapy greatlyreduced the body weight of animals; mice treated in this way showedlighter body weight and more apparent toxic and side effects than thosefrom the negative control group and the polypeptide groups. Theinhibition rates of polypeptide I at high, medium and low doses onheterotransplanted human brain tumor SF763 in nude mice were 60.16%,71.19% and 67.80% respectively. The tumor volume of mice from allpolypeptide groups, including the high-dose group, the medium-dose groupand the low-dose group, exhibited extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide II on heterotransplanted humanbrain tumor SF763 in nude mice is shown in Table 64. The inhibition rateof the taxol group on heterotransplanted human brain tumor SF763 in nudemice was 76.29%, however, this chemotherapy greatly reduced the bodyweight of animals; mice treated in this way showed lighter body weightand more apparent toxic and side effects than those from the negativecontrol group and the polypeptide groups. The inhibition rates ofpolypeptide II at high, medium and low doses on heterotransplanted humanbrain tumor SF763 in nude mice were 65.48%, 75.02% and 70.61%respectively. The tumor volume of mice from the high-dose grouppresented significant difference in contrast with that from the negativecontrol group; the tumor volume of mice from both the medium-dose groupand the low-dose group presented extremely significant difference incontrast with that from the negative control group; meanwhile, animalsfrom the polypeptide groups showed no significant change in body weight,and no obvious toxic and side effects were observed in contrast with thenegative control group.

The inhibition effect of polypeptide III on heterotransplanted humanbrain tumor SF763 in nude mice is shown in Table 65. The inhibition rateof the taxol group on heterotransplanted human brain tumor SF763 in nudemice was 76.29%, however, this chemotherapy greatly reduced the bodyweight of animals; mice treated in this way showed lighter body weightand more apparent toxic and side effects than those from the negativecontrol group and the polypeptide groups. The inhibition rates ofpolypeptide III at high, medium and low doses on heterotransplantedhuman brain tumor SF763 in nude mice were 74.06%, 79.76% and 72.82%respectively. All polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with the negative control group;meanwhile, animals from the polypeptide groups showed no significantchange in body weight, and no obvious toxic and side effects wereobserved in contrast with the negative control group.

Embodiment 25 Test on the Inhibition Effect of Integrin-BlockingPolypeptide I, Polypeptide II and Polypeptide III on HeterotransplantedHuman Rectal Cancer Colo 320 in Nude Mice

The tumor inoculation process and analysis methods were the same asthose mentioned in embodiment 6. Taxol used in the positive controlgroup was administered once every 3 days through tail vein injection,while drugs of all other groups were administered on daily basis throughtail vein injection.

TABLE 66 inhibition effect of polypeptideIon heterotransplanted humanrectal cancer Colo 320 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 20.09 ± 0.63 12 23.22 ± 0.50 12 1.25 ±0.31  — taxol 10 19.96 ± 0.59 8 17.08 ± 0.57 7 0.29 ± 0.07** 76.62%endostar (rh-endostatin) 2.5 20.05 ± 0.70 8 23.05 ± 0.67 8 0.68 ± 0.28 45.41% polypeptide I(high) 3 19.94 ± 0.59 8 20.99 ± 0.66 7 0.51 ± 0.09**59.20% polypeptide I(medium) 1.5 19.88 ± 0.50 8 22.87 ± 0.57 7 0.44 ±0.05** 64.80% polypeptide I(low) 0.75 20.21 ± 0.64 8 23.11 ± 0.61 8 0.52± 0.08** 58.40%

TABLE 67 inhibition effect of polypeptide II on heterotransplanted humanrectal cancer Colo 320 in nude mice dose initial weight initial finalweight final tumor weight tumor inhi- group (mg/kg/time) (g) number (g)number (g) bition rate control — 20.09 ± 0.63 12 23.22 ± 0.50 12 1.25 ±0.31  — taxol 10 19.96 ± 0.59 8 17.08 ± 0.57 7 0.29 ± 0.07** 76.62%endostar (rh-endostatin) 2.5 20.05 ± 0.70 8 23.05 ± 0.67 8 0.68 ± 0.28 45.41% polypeptide II (high) 3 19.88 ± 0.58 8 22.99 ± 0.37 8 0.41 ±0.09** 67.41% polypeptide II (medium) 1.5 19.97 ± 0.66 8 23.10 ± 0.61 80.31 ± 0.03** 75.42% polypeptide II (low) 0.75 20.07 ± 0.54 8 22.85 ±0.61 8 0.35 ± 0.10** 72.26%

TABLE 68 inhibition effect of polypeptide III on heterotransplantedhuman rectal cancer Colo 320 in nude mice dose initial weight initialfinal weight final tumor weight tumor inhi- group (mg/kg/time) (g)number (g) number (g) bition rate control — 20.09 ± 0.63 12 23.22 ± 0.5012 1.25 ± 0.31  — taxol 10 19.96 ± 0.59 8 17.08 ± 0.57 7 0.29 ± 0.07**76.62% endostar (rh-endostatin) 2.5 20.05 ± 0.70 8 23.05 ± 0.67 8 0.68 ±0.28  45.41% polypeptide III(high) 0.75 19.82 ± 0.60 8 23.14 ± 0.48 80.33 ± 0.08** 73.51% polypeptide III(medium) 0.375 19.96 ± 0.58 8 22.93± 0.56 8 0.24 ± 0.05** 80.89% polypeptide III(low) 0.1875 19.87 ± 0.58 822.81 ± 0.60 8 0.37 ± 0.07** 70.34%RESULTS: the inhibition effect of polypeptide I on heterotransplantedhuman rectal cancer Colo 320 in nude mice is shown in Table 66. Theinhibition rate of the taxol group on heterotransplanted human rectalcancer Colo 320 in nude mice was 76.62%, however, this chemotherapygreatly reduced the body weight of animals; mice treated in this wayshowed lighter body weight and more apparent toxic and side effects thanthose from the negative control group and the polypeptide groups. Theinhibition rates of polypeptide I at high, medium and low doses onheterotransplanted human rectal cancer Colo 320 in nude mice were59.20%, 64.80% and 58.40% respectively. All polypeptide groups,including the high-dose group, the medium-dose group and the low-dosegroup, exhibited extremely significant difference in contrast with thenegative control group; meanwhile, animals from the polypeptide groupsshowed no significant change in body weight, and no obvious toxic andside effects were observed in contrast with the negative control group.

The inhibition effect of polypeptide II on heterotransplanted humanrectal cancer Colo 320 in nude mice is shown in Table 67. The inhibitionrate of the taxol group on heterotransplanted human rectal cancer Colo320 in nude mice was 76.62%, however, this chemotherapy greatly reducedthe body weight of animals; mice treated in this way showed lighter bodyweight and more apparent toxic and side effects than those from thenegative control group and the polypeptide groups. The inhibition ratesof polypeptide II at high, medium and low doses on heterotransplantedhuman rectal cancer Colo 320 in nude mice were 67.41%, 75.42% and 72.26%respectively. All polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with the negative control group;meanwhile, animals from the polypeptide groups showed no significantchange in body weight, and no obvious toxic and side effects wereobserved in contrast with the negative control group.

The inhibition effect of polypeptide III on heterotransplanted humanrectal cancer Colo 320 in nude mice is shown in Table 68. The inhibitionrate of the taxol group on heterotransplanted human rectal cancer Colo320 in nude mice was 76.62%, however, this chemotherapy greatly reducedthe body weight of animals; mice treated in this way showed lighter bodyweight and more apparent toxic and side effects than those from thenegative control group and the polypeptide groups. The inhibition ratesof polypeptide III at high, medium and low doses on heterotransplantedhuman rectal cancer Colo 320 in nude mice were 73.51%, 80.89% and 70.34%respectively. All polypeptide groups, including the high-dose group, themedium-dose group and the low-dose group, exhibited extremelysignificant difference in contrast with the negative control group;meanwhile, animals from the polypeptide groups showed no significantchange in body weight, and no obvious toxic and side effects wereobserved in contrast with the negative control group.

Embodiment 26 Test on the In Vivo Immunoprotective Effect of PolypeptideI, Polypeptide II and Polypeptide III on Collagen-Induced Arthritis inMouse Models

Investigating the therapeutic effect of polypeptides disclosed in thepresent invention on mouse collagen-induced arthritis (CIA) by means ofestablishing CIA mouse models. Taking specific, pathogen-free DBA/1 mice(provided by Sino-British SIPPR/BK Lab. Animal Ltd, Shanghai, China;animal production license: SCXK (Shanghai) 2008-0016) as animalsubjects, randomly dividing 7- or 8-week-old male mice with body weightof 18-22 g into the normal control group, model control group,polypeptide I groups including the low-dose (0.2 mg/kg), medium-dose(0.4 mg/kg) and high-dose (0.8 mg/kg) subgroups, polypeptide II groupsincluding the low-dose (0.2 mg/kg), medium-dose (0.4 mg/kg) andhigh-dose (0.8 mg/kg) subgroups, polypeptide III groups including thelow-dose (0.2 mg/kg), medium-dose (0.4 mg/kg) and high-dose (0.8 mg/kg)subgroups, and the (methotrexate 1 mg/kg) positive control group. Apartfrom the normal control group, CIA mouse models were established for alltest groups on day 0. Predissolving chicken cartilage collagen type III(cIII) in 0.1 mol/l acetic acid to prepare 4 mg/ml collagen solution,and then keeping the solution at 4° C. overnight. On day 0 of theexperiment, sufficiently emulsifying type III collagen solution withisovolumetric complete Freund's adjuvant (CFA) containing 4 mg/mlmyeobaeterium tuberculosis (strain H37Rv); anesthetizing DBA/1 mice andintradermically injecting 50 μl emulsion at the tail of each mouse; onday 21 of the experiment, inducing the secondary immune response byintradermically injecting 50 μl emulsion at the tail of each mouseagain; the emulsion used for said secondary immune response is preparedby sufficiently emulsifying 4 mg/ml type III collagen (cIII) andisovolumetric incomplete Freund's adjuvant (IFA). On day 30 of theexperiment, hypodermically administering drugs for each mouse: allpolypeptide groups were divided into low-dose (0.2 mg/kg for polypeptideI and polypeptide II, and 0.1 mg/kg for polypeptide III), medium-dose(0.4 mg/kg for polypeptide I and polypeptide II, and 0.2 mg/mg forpolypeptide III) and high-dose (0.8 mg/kg for polypeptide I andpolypeptide II, and 0.4 mg/kg for polypeptide III) subgroups, twice aday, 10 days in succession; mice from the positive control group wereadministered with methotrexate (1 mg/kg), once every 5 days, three timesin total; mice from the normal control group and model control groupwere administered only with physiological saline on daily basis, 10 daysin succession. During day 21 to day 70 of the experiment, evaluating theimpact of the drugs on CIA mouse models by measuring the body weight,scoring the joint change and examining left and right hind ankles, onceevery 3 days. On day 70 of the experiment, killing mice through cervicaldislocation.

The arthritis was evaluated in accordance with the following criteria:

1) joint scoring: four legs: scoring in terms of level 0 to level 4, 5levels in total. Specifically: 0=no red spot or swelling; 1=small redspot or slight swelling appeared at one of front/hind toe joints); 2=redspot or swelling appeared at more than one front/hind toe joints; 3=pawswelling beneath ankles; 4=paw swelling including ankles. Four feet werescored independently, with 16 as the highest point. Scoring wasconducted during day 21 to day 70 of the experiment, once every 3 days,and recording all the data.2) measuring the diameter of mouse ankles

Measuring the diameter of both left and right ankles (inside-outside)and the thickness of paws of mice with a vernier caliper before themodel establishment and during day 21 to day 70 of the experiment, onceevery 3 days; recording all the data.

The measured data were listed in the form of mean and standard deviation(mean±SD), conducting T-test with SPSS11.0 software for all test groupsand control groups, wherein * referred to p<0.05 and ** p<0.01.

RESULTS: comparing the model mice with the normal mice. On day 0 of theexperiment, the model mice were firstly hypodermically injected at thetail with an emulsion made by collagen and isovolumetric CFA (containingdeactivated myeobaeterium tuberculosis); on day 21 of the experiment,the model mice were again hypodermically injected at the tail with anemulsion made by collagen and isovolumetric IFA; on day 27 of theexperiment, swelling at paws appeared on CIA mice and points forarthritis scoring started increasing; the highest degree of swelling onmodel mice appeared on day 45-60; in addition, the body weight of modelmice stopped increasing since day 35 and even slightly decreased lateron.

Polypeptide I at all doses presented in vivo immunoprotective effect onCIA mouse models. As is shown in Table 69: the swelling degree of pawsin mice from the positive control group, and all high-dose, medium-doseand low-dose polypeptide I groups exhibited extremely significantdifference (p<0.01) in contrast with that from the model control group;the result was statistically significant. The swelling degree of jointsin mice from the positive control group and all high-dose, medium-doseand low-dose polypeptide I groups exhibited extremely significantdifference (p<0.01) in contrast with that from the model control group;the result was statistically significant. The joint scoring of mice fromall high-dose, medium-dose and low-dose polypeptide I was significantlylower (p<0.01) than that from the model control group; the result wasstatistically significant.

TABLE 69 in vivo immunoprotective effect of polypeptide I on CIA mousemodels swelling swelling number dose of paws of joints clinical group(n) (mg/kg) (mm) (mm) scoring normal control 10 — 0.15 ± 0.07** 0.14 ±0.04** 0.00 ± 0.00** model control 10 — 2.12 ± 0.37  1.90 ± 0.40  15.5 ±2.3   positive control 10 1 0.90 ± 0.19** 0.75 ± 0.17** 8.3 ± 1.2**Polypeptide I(high) 10 0.8 1.31 ± 0.26** 1.05 ± 0.31** 11.4 ± 1.6** Polypeptide I(medium) 10 0.4 0.94 ± 0.18** 0.79 ± 0.17** 9.1 ± 1.4**Polypeptide I(low) 10 0.2 1.21 ± 0.22** 0.97 ± 0.23** 9.7 ± 1.5** *referring to p < 0.05, **referring to p < 0.01.

Polypeptide II at all doses presented in vivo immunoprotective effect onCIA mouse models. As is shown in Table 70: the swelling degree of pawsin mice from the positive control group, and all high-dose, medium-doseand low-dose polypeptide II groups exhibited extremely significantdifference (p<0.01) in contrast with that from the model control group;the result was statistically significant. The swelling degree of jointsin mice from the positive control group and all high-dose, medium-doseand low-dose polypeptide II exhibited extremely significant difference(p<0.01) in contrast with that from the model control group; the resultwas statistically significant. The joint scoring of mice from allhigh-dose, medium-dose and low-dose polypeptide II was extremely lower(p<0.01) than that from the model control group; the result wasstatistically significant.

TABLE 70 in vivo immunoprotective effect of polypeptide II on CIA mousemodels swelling swelling number dose of paws of joints clinical group(n) (mg/kg) (mm) (mm) scoring normal control 10 — 0.13 ± 0.03** 0.13 ±0.03** 0.00 ± 0.00** model control 10 — 1.90 ± 0.38  1.86 ± 0.38  15.55± 2.33   positive control 10 1 0.90 ± 0.18** 0.75 ± 0.18** 8.01 ± 1.21**polypeptide II (high) 10 0.8 1.44 ± 0.29** 1.16 ± 0.32** 10.73 ± 1.65** polypeptide II (medium) 10 0.4 0.99 ± 0.20** 0.83 ± 0.21** 9.269 ±1.3**  polypeptide II (low) 10 0.2 1.12 ± 0.32** 0.95 ± 0.24** 9.82 ±1.48** * referring to p < 0.05, **referring to p < 0.01.

Polypeptide III at all doses presented in vivo immunoprotective effecton CIA mouse models. As is shown in Table 71: the swelling degree ofpaws in model mice from the positive control group, and all high-dose,medium-dose and low-dose polypeptide III groups exhibited extremelysignificant difference (p<0.01) in contrast with that from the modelcontrol group; the result was statistically significant. The swellingdegree of joints in mice from the positive control group and allhigh-dose, medium-dose and low-dose polypeptide III exhibited extremelysignificant difference (p<0.01) in contrast with that from the modelcontrol group; the result was statistically significant. The jointscoring of mice from all high-dose, medium-dose and low-dose polypeptideIII was extremely lower (p<0.01) than that from the model control group;the result was statistically significant.

TABLE 71 in vivo immunoprotective effect of polypeptide III on CIA mousemodels swelling swelling number dose of paws of joints clinical group(n) (mg/kg) (mm) (mm) scoring normal control 10 — 0.13 ± 0.03** 0.13 ±0.03** 0.00 ± 0.00** model control 10 — 1.90 ± 0.38  1.86 ± 0.38  15.55± 2.33   positive control 10 1 0.90 ± 0.18** 0.75 ± 0.18** 8.01 ± 1.21**Polypeptide III(high) 10 0.4 1.23 ± 0.25** 1.05 ± 0.26** 10.41 ± 1.56** polypeptide III(medium) 10 0.2 0.85 ± 0.17** 0.68 ± 0.19** 9.13 ± 1.37**polypeptide III(low) 10 0.1 1.03 ± 0.21** 0.92 ± 0.27** 9.73 ± 1.46** *referring to p < 0.05, **referring to p < 0.01.CONCLUSION: polypeptide I, polypeptide II and polypeptide III havetherapeutic effect on collagen-induce arthritis in mice.

Embodiment 27 Test on the In Vivo Immunoprotective Effect of PolypeptideI, Polypeptide II and Polypeptide III on Aduvant Arthritis in Rat Models

Investigating the therapeutic effect of polypeptides disclosed in thepresent invention on adjuvant-induce arthritis (AIA) in rats by means ofestablishing AIA rat models. Taking specific, pathogen-free SD rats(provided by Sino-British SIPPR/BK Lab. Animal Ltd, Shanghai, China;animal production license: SCXK (Shanghai) 2008-0016) as animalsubjects, randomly dividing male rats with body weight of 140-160 g intothe normal control group, model control group, polypeptide I groupsincluding the low-dose (0.4 mg/kg), medium-dose (0.8 mg/kg) andhigh-dose (1.6 mg/kg) subgroups, polypeptide II groups including thelow-dose (0.4 mg/kg), medium-dose (0.8 mg/kg) and high-dose (1.6 mg/kg)subgroups, polypeptide III groups including the low-dose (0.2 mg/kg),medium-dose (0.4 mg/kg) and high-dose (0.8 mg/kg) subgroups, and the(methotrexate 1 mg/kg) positive control group. Apart from the normalcontrol group, AIA rat models were established for all test groups onday 0 by injecting at the left hind paw of all rats with 0.08 ml CFAcontaining 10 mg/ml deactivated myeobaeterium tuberculosis (strainH37RA). On day 10 of the experiment, hypodermically administering drugsfor each rat: all polypeptide groups were divided into low-dose (0.4mg/kg for polypeptide I and polypeptide II, and 0.2 mg/kg forpolypeptide III), medium-dose (0.8 mg/kg for Polypeptide I andPolypeptide II, and 0.4 mg/kg for polypeptide III) and high-dose (1.6mg/kg for polypeptide I and polypeptide II, and 0.8 mg/kg forpolypeptide III) subgroups, twice a day, 10 days in succession; ratsfrom the positive control group were administered with methotrexate (1mg/kg), once every 5 days, three times in total; rats from the normalcontrol group and model control group were administered only withphysiological saline on daily basis, 10 days in succession. On day 8,11, 14, 17, 20, 23 and 26 of the experiment, evaluating the impact ofthe drugs on AIA rat models by examining the diameter of both left andright hind ankles.

The arthritis was evaluated in accordance with the following criteria:

1) joint scores: four legs: scoring in terms of level 0 to level 4, 5levels in total. Specifically: 0=no red spot or swelling; 1=small redspot or slight swelling appeared at one of front/hind toe joints); 2=redspot or swelling appeared at more than one front/hind toe joints; 3=pawswelling beneath ankles; 4=paw swelling including ankles. Four feet werescored independently, with 16 as the highest point.

Scoring joints on day 8, 11, 14, 17, 20, 23 and 26 of the experiment andrecording all the data.

2) measuring the diameter of rat ankles

Measuring the diameter of both left and right ankles (inside-outside)and the thickness of paws of mice with a vernier caliper before themodel establishment and during day 11 to day 23 of the experiment, onceevery 26 days; recording all the data.

The measured data were listed in the form of mean and standard deviation(mean±SD), conducting T-test with SPSS11.0 software for all test groupsand control groups, wherein * referred to p<0.05 and ** p<0.01.

RESULTS: comparing the model rats with the normal rats. The primaryarthritis appeared at the left hind paw of model rats soon afterinjection of CFA containing deactivated myeobaeterium tuberculosis atthe left hind paw, along with apparent swelling and ulceration; thesecondary arthritis appeared at the right high paw about 10 days later,with increasingly high scores; meanwhile, apparent angiogenesis occurredat rat ears, with obvious redness and swelling; swelling also appearedat tail joints.

Polypeptide I at all doses presented in vivo immunoprotective effect onAIA rat models. As is shown in Table 72: the diameter of the left hindpaw of rats from both the positive control group and polypeptide Imedium-dose group presented extremely significant difference (p<0.01) incontrast with that from the model control group; the diameter of theleft hind paw of rats from both polypeptide I low-dose group andpolypeptide I high-dose group presented significant difference (p<0.05)in contrast with that from the model control group; the result wasstatistically significant. The diameter of the right hind paw of ratsfrom the positive control group, as well as polypeptide I low-dose,medium-dose and high-dose groups presented significant difference(p<0.05) in contrast with that from the model control group. The jointscoring of rats from all high-dose, medium-dose and low-dose groups ofpolypeptide I was significantly lower (p<0.05) than that from the modelcontrol group; the result was statistically significant.

TABLE 72 in vivo immunoprotective effect of polypeptide I on AIA ratmodels swelling of swelling of number dose left paws right paws clinicalgroup (n) (mg/kg) (mm) (mm) scoring normal control 10 — 0.79 ± 0.18** 0.56 ± 0.08**  0.0 ± 0.0** model control 10 — 7.11 ± 1.4   3.38 ± 0.94 13.5 ± 2.6  positive control 10 1 3.52 ± 0.72**  0.63 ± 0.19** 4.8 ±1.0* polypeptide I(high) 10 1.6 4.81 ± 0.95*  1.35 ± 0.30* 7.0 ± 1.2*polypeptide I(medium) 10 0.8 3.83 ± 0.76** 0.94 ± 0.18* 5.5 ± 1.0*polypeptide I(low) 10 0.4 4.25 ± 0.85*  1.36 ± 0.31* 7.1 ± 1.1**referring to p < 0.05, **referring to p < 0.01.

Polypeptide II at all doses presented in vivo immunoprotective effect onAIA rat models. As is shown in Table 73: the diameter of the left hindpaw of rats from both the positive control group and polypeptide IImedium-dose group presented extremely significant difference (p<0.01) incontrast with that from the model control group; the diameter of theleft hind paw of rats from both polypeptide II low-dose group andpolypeptide II high-dose group presented significant difference (p<0.05)in contrast with that from the model control group; the result wasstatistically significant. The swelling degree of the right paw of ratsfrom the positive control group, as well as polypeptide II low-dose,medium-dose and high-dose groups presented significant difference(p<0.05) in contrast with that from the model control group. The jointscoring of rats from all high-dose, medium-dose and low-dose groups ofpolypeptide II was significantly lower (p<0.05) than that from the modelcontrol group; the result was statistically significant.

TABLE 73 in vivo immunoprotective effect of polypeptide II on AIA ratmodels swelling of swelling of number dose left paw right paw clinicalgroup (n) (mg/kg) (mm) (mm) scoring normal control 10 — 0.90 ± 0.17**0.38 ± 0.11**  0.00 ± 0.00** model control 10 — 7.01 ± 1.42  3.21 ±0.69  13.11 ± 2.62  positive control 10 1 3.51 ± 0.77** 0.59 ± 0.17**5.02 ± 1.11* polypeptide II (high) 10 1.6 4.69 ± 0.94*  1.39 ± 0.36* 7.21 ± 1.44* polypeptide II (medium) 10 0.8 3.88 ± 0.75** 0.82 ± 0.24* 5.57 ± 1.25* polypeptide II (low) 10 0.4 4.42 ± 0.86*  1.1 ± 0.23* 6.34± 1.22* *referring to p < 0.05, **referring to p < 0.01.CONCLUSION: polypeptide II has therapeutic effect on adjuvant-inducedarthritis in rats

Polypeptide III at all doses presented in vivo immunoprotective effecton AIA rat models. As is shown in Table 74: the diameter of the lefthind paw of rats from both the positive control group and polypeptideIII medium-dose group presented extremely significant difference(p<0.01) in contrast with that from the model control group; thediameter of the left hind paw of rats from both polypeptide III low-dosegroup and polypeptide I high-dose group presented significant difference(p<0.05) in contrast with that from the model control group; the resultwas statistically significant. The diameter of the right hind paw ofrats from the positive control group, as well as polypeptide IIIlow-dose, medium-dose and high-dose groups presented significantdifference (p<0.05) in contrast with that from the model control group.The joint scoring of rats from all high-dose, medium-dose and low-dosegroups of polypeptide III was significantly lower (p<0.05) than thatfrom the model control group; the result was statistically significant.

TABLE 74 in vivo immunoprotective effect of polypeptide III on AIA ratmodels swelling of swelling of number dose left paw right paw clinicalgroup (n) (mg/kg) (mm) (mm) scoring normal control 10 — 0.90 ± 0.17** 0.38 ± 0.11**  0.00 ± 0.00** model control 10 — 7.01 ± 1.42  3.21 ±0.69  13.11 ± 2.62  positive control 10 1 3.51 ± 0.77**  0.59 ± 0.17**5.02 ± 1.11* polypeptide III(high) 10 0.8 4.65 ± 0.94*  1.17 ± 0.26*6.33 ± 1.20* polypeptide III(medium) 10 0.4 3.72 ± 0.76** 0.73 ± 0.21*5.29 ± 1.04* polypeptide IIII(low) 10 0.2 4.0 ± 0.74* 1.09 ± 0.28* 5.69± 1.12* *referring to p < 0.05, **referring to p < 0.01.CONCLUSION: polypeptide I, polypeptide II and polypeptide III havetherapeutic effect on adjuvant-induced arthritis in rats.

What is claimed is:
 1. A method for treating rheumatoid arthritis, themethod comprising the steps of: preparing a pharmaceutical preparationcomprising an integrin-blocking polypeptide consisting of the amino acidsequence of SEQ ID NO: 2 or comprising the amino acid sequence of SEQ IDNO: 3; and administering to a patient suffering from rheumatoidarthritis the pharmaceutical preparation comprising theintegrin-blocking polypeptide.
 2. The method of claim 1, wherein theintegrin-blocking polypeptide comprises the amino acid sequence of SEQID NO:
 3. 3. The method of claim 1, wherein the pharmaceuticalpreparation further comprises an adjuvant covalently connected to theintegrin-blocking polypeptide.
 4. The method of claim 3, wherein theadjuvant is selected from the group consisting of bovine serum albumin(BSA), human serum albumin (HSA) and polyethylene glycol (PEG).
 5. Themethod of claim 1, wherein the step of administering the pharmaceuticalpreparation occurs via a route of administration selected from the groupconsisting of hypodermic injection, intramuscular injection, intravenousinjection, intravenous drip, oral administration and nasal spray.